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Cell adhesion molecules regulate a variety of endothelial cell functions such as migration, response to inflammation, and angiogenesis. Recently, activated leukocyte cell adhesion molecule (ALCAM), a member of the Ig superfamily, has been detected in the primitive subsets of hematopoietic cells and endothelial cells during embryogenesis. ALCAM supports the development of hematopoietic cells as well as enhancing capillary tube formation in vitro. Here, we isolated a novel soluble isoform of ALCAM (sALCAM) that is produced via alternative splicing. sALCAM contains the single amino-terminal Ig-like domain of ALCAM and lacks a transmembrane domain. When expressed in cultured cells, sALCAM was properly secreted into the media. Both ALCAM and sALCAM are expressed in a variety of cultured human endothelial cells. Notably, their transcripts were differentially regulated in human microvascular endothelial cells (HMVEC) upon tumor necrosis factor-α stimulation. ALCAM significantly enhanced tube formation of endothelial-like yolk sac cells on Matrigel, whereas it inhibited their migration in vitro. sALCAM completely abolished these effects of ALCAM. Furthermore, sALCAM enhanced migration of mock-transfected endothelial-like yolk sac cells that do not express ALCAM, indicating that sALCAM has an independent effect on cell migration in addition to modulating ALCAM function. In addition, sALCAM significantly enhanced migration of HMVEC, whereas it inhibited tube formation of HMVEC on Matrigel. sALCAM demonstrated an ability to bind ALCAM and partially inhibited ALCAM-ALCAM homophilic interactions. Taken together, these data characterize a novel soluble isoform of ALCAM that may have ALCAM-dependent and ALCAM-independent functions, providing further insights regarding the role of this adhesion molecule in the regulation of endothelial cell function. Cell adhesion molecules regulate a variety of endothelial cell functions such as migration, response to inflammation, and angiogenesis. Recently, activated leukocyte cell adhesion molecule (ALCAM), a member of the Ig superfamily, has been detected in the primitive subsets of hematopoietic cells and endothelial cells during embryogenesis. ALCAM supports the development of hematopoietic cells as well as enhancing capillary tube formation in vitro. Here, we isolated a novel soluble isoform of ALCAM (sALCAM) that is produced via alternative splicing. sALCAM contains the single amino-terminal Ig-like domain of ALCAM and lacks a transmembrane domain. When expressed in cultured cells, sALCAM was properly secreted into the media. Both ALCAM and sALCAM are expressed in a variety of cultured human endothelial cells. Notably, their transcripts were differentially regulated in human microvascular endothelial cells (HMVEC) upon tumor necrosis factor-α stimulation. ALCAM significantly enhanced tube formation of endothelial-like yolk sac cells on Matrigel, whereas it inhibited their migration in vitro. sALCAM completely abolished these effects of ALCAM. Furthermore, sALCAM enhanced migration of mock-transfected endothelial-like yolk sac cells that do not express ALCAM, indicating that sALCAM has an independent effect on cell migration in addition to modulating ALCAM function. In addition, sALCAM significantly enhanced migration of HMVEC, whereas it inhibited tube formation of HMVEC on Matrigel. sALCAM demonstrated an ability to bind ALCAM and partially inhibited ALCAM-ALCAM homophilic interactions. Taken together, these data characterize a novel soluble isoform of ALCAM that may have ALCAM-dependent and ALCAM-independent functions, providing further insights regarding the role of this adhesion molecule in the regulation of endothelial cell function. The major component of blood vessels is a single layer of endothelial cells and smooth muscle cells or mural cells. Secreted and membrane proteins expressed in endothelial cells and smooth muscle cells play particular roles in the physiology and pathophysiology of blood vessels. To identify secreted and membrane proteins expressed in endothelial cells, we performed signal sequence trap screening using a retrovirus-based expression cDNA library of human microvascular endothelial cells. One of the genes isolated encoded a novel putative secretory isoform of activated leukocyte cell adhesion molecule (ALCAM), 1The abbreviations used are: ALCAM, activated leukocyte cell adhesion molecule; sALCAM, soluble isoform of ALCAM; IL, interleukin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; CHO, Chinese hamster ovary; HMVEC, human lung microvascular endothelial cells; TNF, tumor necrosis factor; PMA, phorbol 12-myristate 13-acetate; sCAM, soluble cell adhesion molecules. 1The abbreviations used are: ALCAM, activated leukocyte cell adhesion molecule; sALCAM, soluble isoform of ALCAM; IL, interleukin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; CHO, Chinese hamster ovary; HMVEC, human lung microvascular endothelial cells; TNF, tumor necrosis factor; PMA, phorbol 12-myristate 13-acetate; sCAM, soluble cell adhesion molecules. also known as BEN, SC1, DM-GRASP, MEMD, HCA, and CD166 (1Pourquie O. Coltey M. Thomas J. L. Le Douarin N. M. Development (Camb. ). 1990; 109: 743-752PubMed Google Scholar, 2Burns F. R. von Kannen S. Guy L. Raper J. A. Kamholz J. Chang S. Neuron. 1991; 2: 209-220Abstract Full Text PDF Scopus (184) Google Scholar, 3Tanaka H. Matsui T. Agata A. Tomura M. Kubota I. McFarland K. C. Kohr B. Lee A. Phillips H. S. Shelton D. L. Neuron. 1991; 7: 535-545Abstract Full Text PDF PubMed Scopus (185) Google Scholar, 4Degen W. G. van Kempen L. C. Gijzen E. G. van Groningen J. J. van Kooyk Y. Bloemers H. P. Swart G. W. Am. J. Pathol. 1998; 152: 805-813PubMed Google Scholar, 5Uchida N. Yang Z. Combs J. Pourquie O. Nguyen M. Ramanathan R. Fu J. Welply A. Chen S. Weddell G. Sharma A. K. Leiby K. R. Karagogeos D. Hill B. Humeau L. Stallcup W. B. Hottman R. Tsukamoto A. S. Gearing D. P. Peault B. Blood. 1997; 89: 2706-2716Crossref PubMed Google Scholar, 6Patel D. D. Wee S. F. Whichard L. P. Bowen M. A. Pesando J. M. Aruffo A. Haynes B. F. J. Exp. Med. 1995; 181: 1563-1568Crossref PubMed Scopus (126) Google Scholar). ALCAM is a type I membrane protein that belongs to the Ig superfamily, and it has five extracellular variable type and constant type Ig domains and a single transmembrane domain. Human ALCAM was initially isolated as a ligand of CD6, a cell surface receptor belonging to the scavenger receptor cysteine-rich protein superfamily (6Patel D. D. Wee S. F. Whichard L. P. Bowen M. A. Pesando J. M. Aruffo A. Haynes B. F. J. Exp. Med. 1995; 181: 1563-1568Crossref PubMed Scopus (126) Google Scholar). CD6 is expressed on the surface of mature T cell and chronic B cell lymphocytic leukemia. Expression of CD6 on T cells is up-regulated following activation, and previous reports suggest that CD6 modulates T cell receptor signaling (7Aruffo A. Bowen M. A. Patel D. D. Haynes B. F. Starling G. C. Gebe J. A. Bajorath J. Immunol. Today. 1997; 18: 498-504Abstract Full Text PDF PubMed Scopus (129) Google Scholar). Therefore, binding of ALCAM to CD6 suggests that ALCAM may be involved in immune and/or inflammatory responses. In addition, ALCAM has been detected in a variety of cell types where it participates in heterophilic interactions with unknown ligands as well as homophilic interactions, suggesting that ALCAM has varied functions (8DeBernardo A. P. Chang S. J. Cell Biol. 1996; 133: 657-666Crossref PubMed Scopus (71) Google Scholar, 9Swart G. W. Eur. J. Cell Biol. 2002; 81: 313-321Crossref PubMed Scopus (199) Google Scholar). In fact, BEN/SC1/DM-GRASP, a chicken homologue of ALCAM, is expressed in the nervous systems and plays a role in axogenesis, neurite elongation, and synapse formation (2Burns F. R. von Kannen S. Guy L. Raper J. A. Kamholz J. Chang S. Neuron. 1991; 2: 209-220Abstract Full Text PDF Scopus (184) Google Scholar, 10DeBernardo A. P. Chang S. Dev. Biol. 1995; 169: 65-75Crossref PubMed Scopus (31) Google Scholar, 11Chedotal A Pourquie O. Sotelo C. Eur. J. Neurosci. 1995; 7: 198-212Crossref PubMed Scopus (82) Google Scholar). Although ALCAM is expressed in a variety of cell types and tissues, it is certainly expressed in subsets of cells involved in dynamic growth and migration, including developing neuronal cells, hematopoietic cells. Although its physiological function is still unclear, its unique expression pattern suggests that ALCAM is involved in cell differentiation and migration. Recently ALCAM expression has been detected in the fairly primitive subsets of hematopoietic cells and endothelial cells during embryogenesis (12Ohneda O. Ohneda K. Arai F. Lee J. Miyamoto T. Fukushima Y. Dowbenko D. Lasky L. A. Suda T. Blood. 2001; 98: 2134-2142Crossref PubMed Scopus (120) Google Scholar). ALCAM supports the development of hematopoietic progenitor cells and enhances the capillary tube formation of endothelial cells, suggesting that ALCAM is involved in both vasculogenesis and angiogenesis. Here we isolated a novel soluble isoform of ALCAM (sALCAM) that is produced via alternative splicing. sALCAM demonstrated an ALCAM-independent effect in endothelial cell assays as well as a regulatory effect on ALCAM function. sALCAM mRNA expression is differentially regulated from that of ALCAM upon inflammatory stimulation. These data suggest that sALCAM may modulate endothelial function through both ALCAM-dependent and ALCAM-independent pathways. Cloning of sALCAM—Signal sequence trap was performed as previously described (13Kojima T. Kitamura T. Nat. Biotechnol. 1999; 17: 487-490Crossref PubMed Scopus (77) Google Scholar). Briefly, a library was constructed in the retrovirus vector pMX-SST employing cDNA derived from mRNA isolated from cultured human lung microvascular endothelial cells. The pMX-SST vector has a sequence encoding the constitutively active thrombopoietin receptor (MPL) downstream of the cloning site. When constitutive active MPL is expressed on the plasma membrane, it transmits a proliferative signal. The cDNA library was transfected into Phoenix-Eco packaging cells, and retroviruses carrying cDNA were collected. Interleukin-3 (IL-3) -dependent pro-B (Ba/F3) cells were infected with retrovirus followed by seeding on ten 96-multiwell plates (960 wells) in the absence of IL-3. Only Ba/F3 cells expressing the constitutively active MPL at the plasma membrane were able to grow in the absence of IL-3. IL-3-independent growth of Ba/F3 cells was observed in about 300 wells. Genomic DNA was extracted from these Ba/F3 clones, and PCR was performed using genomic DNA as a template and primers specific for the cloning vector. After electrophoresis of the PCR products, DNA was recovered and subjected to sequencing. Mouse sALCAM was identified through sequence data base searches (BC027280 and NT₀96987. 1 were used). The nucleotide sequence of the 3′-ends of human and mouse sALCAM was determined by 3′-rapid amplification cDNA ends using total RNA from human microvascular endothelial cells and the mouse endothelial cell line C166 cells, respectively. Semiquantitative Reverse Transcription-PCR—Total RNA was extracted from cells using TRIzol (Invitrogen). cDNA was synthesized from 2. 5 μg of total RNA using the SuperScript first-strand synthesis system (Invitrogen). The forward primer 5′-GCTAGTAACTGAGGACAACGTG-3′ and the reverse primer 5′-GAGCTTCTTATTCCTTCGGGCTG-3′ were used for ALCAM amplification. The forward primer 5′-ATACCTTGCCGACTTGACGTACCT-3′ and the reverse primer 5′-AAAGAACATGGTCTGGTACTGGCC-3′ were used for sALCAM amplification. The forward primer 5′-CCTTCATTGACCTCAACTACATGG-3′ and the reverse primer 5′-CCTGCTTCACCACCTTCTTGAT-3′ were used for GAPDH amplification. PCR conditions were optimized so that quantification of amplified material was in the linear phase of amplification. After 3 min of incubation at 95 °C, a PCR cycle of 95 °C for 30 s, 58 °C for 30 s and 72 °C for 45 s was used. PCR cycles of 28 times, 30 times, and 26 times were performed for amplification of ALCAM, sALCAM, and GAPDH, respectively. The size of the PCR product was 543 bp, 340 bp, and 687 bp for ALCAM, sALCAM and GAPDH, respectively. of sALCAM and of human sALCAM was into the expression vector and transfected into cells using (Invitrogen). growth were and cells were further for the were and subjected to of sALCAM using the was by protein on the of using as a in this was for in was transfected into cells in the and cells were in the Cell and were at °C for 3 in the or absence of as by the was performed using as described previously K. N. M. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). Cell and yolk sac cell was cultured as described previously T. Yang K. T. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). The of human ALCAM was into and transfected into cells using of were in the of were by of cells were cultured as described previously K. N. Y. K. M. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). of ALCAM in cells were as for the cells and Human lung microvascular endothelial cells (HMVEC) were from and cultured on HMVEC were cultured in and in the for followed by with the of for the and the and were to in A was in the of the with a and cells were with The of cells were and cells were in the in the or absence of 300 After of of cells were and the migration of the cells at the was for at five for the with for a were used. were into the of migration with When HMVEC were were with cells were on the in of migration in the or absence of sALCAM at the cells migration, was for HMVEC migration endothelial growth were used to migration. After of cells on the were with and cells on the surface were with followed by with were from the and and cells were a in at five independent In on assays on were performed in plates with of Matrigel. cells were on in growth in the or absence of 300 sALCAM and for human microvascular endothelial cells were on in the or absence of sALCAM and for in were in independent sALCAM of human ALCAM and encoding a at its was into a expression vector that the K. N. Y. K. M. M. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google or vector was transfected into cells using (Invitrogen). cells were with or sALCAM in the at °C for 30 were with times and in the After the of protein 30 μg of cell was subjected to Cell was performed as described previously K. T. K. M. Yang J. T. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). Briefly, and cells were with and cells were in to a of Cell were in the or absence of or sALCAM in with on the for min at were on a and the of cells were were using was data are as as of secreted and transmembrane proteins play roles in endothelial cell we the of signal sequence trap using mRNA from HMVEC to genes encoding such novel and of demonstrated to ALCAM. The nucleotide sequence of the was to human ALCAM the the sequence the an was identified such that this encoded a of ALCAM. protein have to amino-terminal ALCAM and be of a variable type domain was encoded transmembrane domain in this of ALCAM, we it soluble ALCAM also identified cDNA in the data base and that sALCAM, of the genomic of human and mouse sALCAM that sALCAM mRNA is produced from the via alternative To the of sALCAM, we performed 3′-rapid amplification cDNA ends using total RNA from human and mouse endothelial cells. Both human and mouse sALCAM transcripts were to in 3 for and the signal was observed the 3′-ends of both human and mouse not sALCAM Expression of the cell of human ALCAM and sALCAM expression using Both ALCAM and sALCAM were expressed in a variety of cultured human cells, including endothelial cells and smooth muscle cells that PCR cycles were to of sALCAM DNA were for ALCAM, it is that ALCAM is expressed at sALCAM in cell types we further their regulated expression upon of by inflammatory sALCAM and sALCAM expression was at and stimulation. was the that ALCAM expression and was its effect was not observed at and the sALCAM expression was up-regulated with and its effect 12-myristate expression of both ALCAM and sALCAM whereas endothelial growth not a These data suggest that the for alternative transcripts may be regulated we sALCAM is a secreted this sALCAM was expressed in cells by A was at for the of sALCAM was detected in the as well as cell indicating that sALCAM is secreted The of sALCAM in the was from sALCAM in the cell both of were the sALCAM is to have we that sALCAM Therefore, we the cell and the with an F. After the sALCAM in both cell and the by indicating that sALCAM is further we sALCAM protein from cell and the was by sALCAM Cell the functions of ALCAM and sALCAM, we endothelial-like yolk sac cells expressing ALCAM. cells not express ALCAM not the role of ALCAM and sALCAM in migration with and ALCAM expression is to subsets of cells involved in dynamic growth and/or migration, including immune and tumor we ALCAM to cell migration G. W. Eur. J. Cell Biol. 2002; 81: 313-321Crossref PubMed Scopus (199) Google Scholar). cells expressing ALCAM migration mock-transfected cells by both assays A and addition of sALCAM cell migration not of also of suggesting that sALCAM has an ALCAM-independent effect on cell migration Notably, sALCAM a effect on migration, whereas sALCAM demonstrated a effect on migration. with sALCAM, was of migration and suggesting that at this sALCAM the ALCAM-dependent effect on cell migration. The ALCAM-independent effect of sALCAM was not observed in the of in this with the ALCAM expressing cells in a tube formation on Matrigel. significantly enhanced tube formation with of tube formation was also abolished by sALCAM and we sALCAM has a effect on human endothelial cells. the migration and tube formation of HMVEC, express ALCAM, in the or absence of to the with sALCAM enhanced HMVEC migration in a and sALCAM effect sALCAM also inhibited tube formation of HMVEC on B and These data suggest that ALCAM also has a effect on endothelial cell migration supports in tube and that sALCAM has an ability to modulate endothelial cell function. sALCAM a on ALCAM sALCAM has an ability to bind ALCAM, we cells expressing and the cells with was detected by binding of sALCAM was observed at at binding of sALCAM was observed to with cells, suggesting that sALCAM has an ability to bind ALCAM we cell assays using cells expressing ALCAM After 30 min of were observed in whereas was observed in mock-transfected cells When cells were with sALCAM, were significantly cell observed for the cells, whereas sALCAM not the formation of the cell B and These suggest that sALCAM has a regulatory effect on ALCAM-ALCAM homophilic have described the and of a novel soluble isoform of ALCAM. sALCAM has a single variable type Ig domain that is to the amino-terminal Ig domain of ALCAM. the amino-terminal Ig domain of ALCAM is the binding for both ALCAM-ALCAM homophilic and heterophilic interactions, it was that sALCAM has a regulatory role in ALCAM function (7Aruffo A. Bowen M. A. Patel D. D. Haynes B. F. Starling G. C. Gebe J. A. Bajorath J. Immunol. Today. 1997; 18: 498-504Abstract Full Text PDF PubMed Scopus (129) Google Scholar, M. A. Aruffo Bajorath J. PubMed Scopus Google Scholar, M. A. Bajorath J. M. D. J. Starling G. C. Aruffo A. Eur. J. Immunol. 1997; PubMed Scopus Google Scholar, Kempen L. C. J. M. W. G. R. Bloemers H. P. Swart G. W. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). that sALCAM modulates endothelial cell function through both ALCAM-dependent and ALCAM-independent and that its expression is differentially regulated upon inflammatory stimulation. ALCAM is a member of the Ig superfamily and has variable type Ig domains followed by constant type Ig domains in its extracellular The extracellular or of adhesion molecules are for specific ligand binding and with cell surface proteins and extracellular has been that these be from the cell by to soluble cell adhesion molecules A. C. A. J. Immunol. 1996; PubMed Scopus Google Scholar). Although the physiological roles of still to be their to bind the ligands suggest that as molecules or as that ligand A. C. A. J. Immunol. 1996; PubMed Scopus Google Scholar). it has been that play particular roles in cell migration, and tumor growth A. C. A. J. Immunol. 1996; PubMed Scopus Google Scholar, 1995; PubMed Scopus Google Scholar, L. L. M. 1998; Google Scholar, G. 1999; Google Scholar, M. 2001; Google Scholar). Although is the for the formation of sCAM, are produced by alternative such as that with and J. Biol. 1990; Full Text PDF PubMed Google Scholar, and M. J. Biol. Scholar, A. J. A. C. J. Biol. Full Text PDF PubMed Google Scholar). Both soluble and are produced by a single encoding a transmembrane domain. the of extracellular domain. In it is also produced via alternative sALCAM contains a of of ALCAM. Furthermore, this is the that expression of a is differentially regulated from that of its demonstrated and of sALCAM expression in HMVEC, it effect on ALCAM is a sALCAM may play an role in the response of endothelial cells to ALCAM is a ligand for CD6 that is involved in T cell activation, and ALCAM expression is in T cells following (7Aruffo A. Bowen M. A. Patel D. D. Haynes B. F. Starling G. C. Gebe J. A. Bajorath J. Immunol. Today. 1997; 18: 498-504Abstract Full Text PDF PubMed Scopus (129) Google Scholar). of ALCAM have been detected in cells in of in Whichard L. P. Patel D. D. 1998; PubMed Scopus Google Scholar). These suggest that ALCAM is involved in the pathophysiology of Furthermore, we identified that ALCAM expression was up-regulated in the from mouse not that plays roles in ALCAM and sALCAM may play particular roles in the development of J. L. N. Y. PubMed Scopus Google Scholar, R. N. J. Med. 1999; PubMed Scopus Google Scholar, 2002; PubMed Scopus Google Scholar). the PMA, a protein both ALCAM and sALCAM expression in it has been that protein plays a role in adhesion J. M. van Kooyk Y. Biol. PubMed Scopus (71) Google Scholar, J. M. F. J. Cell PubMed Scopus Google Scholar). adhesion in cells by protein not ALCAM expression in cells, indicating that of ALCAM expression in HMVEC is a effect of is known to in endothelial cells, of cell adhesion may to is to the physiological of ALCAM and sALCAM by ALCAM is expressed in cells such as neuronal cells, hematopoietic progenitor cells, and cells, we that ALCAM cell G. W. Eur. J. Cell Biol. 2002; 81: 313-321Crossref PubMed Scopus (199) Google Scholar). indicating that ALCAM has an effect on migration. of sALCAM cell migration of not also suggesting that sALCAM has an ALCAM-independent effect on cell In the of these sALCAM enhanced the migration of human endothelial cells, HMVEC, in a Notably, sALCAM effect on cell migration of and HMVEC at whereas sALCAM demonstrated the effect for that with sALCAM, to and HMVEC expressed ALCAM, sALCAM reverse the ALCAM-dependent effect on cell migration. sALCAM was to the binding to ALCAM and the effect on ALCAM-ALCAM homophilic we that the ALCAM-dependent effect on cell migration is via ALCAM heterophilic with an unknown ligand that be inhibited by sALCAM that to ALCAM-ALCAM homophilic interactions. is to these it has been that ALCAM enhances the capillary tube formation of a mouse endothelial cell we tube formation of on (12Ohneda O. Ohneda K. Arai F. Lee J. Miyamoto T. Fukushima Y. Dowbenko D. Lasky L. A. Suda T. Blood. 2001; 98: 2134-2142Crossref PubMed Scopus (120) Google Scholar). demonstrated enhanced tube formation as with suggesting that ALCAM has a effect on capillary tube formation of endothelial cells of endothelial cell sALCAM this effect of ALCAM on tube formation and inhibited tube formation of These data that sALCAM has an effect on endothelial cell tube it this effect is by ALCAM by an ALCAM-independent effect of sALCAM, or through both types of pathways. ALCAM is expressed in human cell W. G. van Kempen L. C. Gijzen E. G. van Groningen J. J. van Kooyk Y. Bloemers H. P. Swart G. W. Am. J. Pathol. 1998; 152: 805-813PubMed Google Scholar). is also expressed in growth phase human whereas the of and do not express ALCAM Kempen L. C. van J. J. van Bloemers H. P. Swart G. W. Am. J. Pathol. Full Text Full Text PDF PubMed Scopus Google Scholar). it has been that expression of ALCAM cell by ALCAM Kempen L. C. F. M. C. M. Bloemers H. P. Swart G. W. J. Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, cell in and and of cells. Therefore, adhesion a in the from tumor growth to the in Although we have not sALCAM expression in human it is to that sALCAM may the of by cell the amino-terminal Ig domain of ALCAM is the binding for ALCAM-ALCAM homophilic sALCAM is to with the amino-terminal Ig domain of ALCAM Kempen L. C. J. M. W. G. R. Bloemers H. P. Swart G. W. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). sALCAM partially the cell by ALCAM-ALCAM homophilic at whereas sALCAM to such that sALCAM not sALCAM demonstrated binding to ALCAM, sALCAM may ALCAM-ALCAM homophilic via binding to ALCAM are for the of sALCAM is not able to the of the Ig domain where it the and/or binding of sALCAM to ALCAM is that of ALCAM to ALCAM. cell by ALCAM homophilic of ALCAM through its constant type Ig domains is also Kempen L. C. J. M. W. G. R. Bloemers H. P. Swart G. W. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). the of ALCAM using an in to cell this not the binding of amino-terminal Ig domain. Therefore, it is also that sALCAM ALCAM-ALCAM homophilic interactions through with the function of Ig is to this including Ig domain function of ALCAM is by In we have isolated a novel soluble isoform of ALCAM. ALCAM-dependent and ALCAM-independent effects and differentially regulated suggest that sALCAM is a physiological of endothelial cell function and that sALCAM the of ALCAM in and/or adhesion and used sALCAM protein to data Therefore, of sALCAM including its for a of ALCAM function. Kitamura for providing the pMX-SST for providing a of signal sequence and for providing the Phoenix-Eco packaging cells.
Ikeda et al. (Thu,) studied this question.