Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

Figures

• 

  Figure 1. Different intensity degrees of vascular/perivascular expression of CD13 in soft tissue sarcomas: D496.16, intensity score 0; D449.16, score 1; D933.16, score 2; D516.16, score 3 (original magnification 200×).

• 

  Figure 2. Different intensity degrees of tumoral expression of CD13 in soft tissue sarcomas: D439.16, intensity score 1; D433.16, score 2; D455.16, score 3 (original magnification 100×).

• 

  Figure 3. Immunofluorescence stainings. Immunofluorescence stainings showing vascular/perivascular CD13 positivity (A) and partial CD13 expression by the tumor cells (B). (C) CD163/CD13 immunofluorescence documents co-expression of CD13 on CD163-positive intralesional macrophages along with clearly discernible expression of CD13 by non-CD163 positive tumor cells (original magnification 600×).

• 

  Figure 4. Prognostic impact of CD13 expression in a group of 97 STS patients. Colored areas represent 95% confidence intervals. A and C represent survival curves in correlation with tumor cell CD13 staining; B and D represent survival curves in correlation with vascular/perivascular cell CD13 staining.

• 

  Figure 5. Prognostic impact of CD13 expression in a subgroup of STS patients without synovial sarcoma and leiomyosarcoma. For further details, see Figure 4.

• 

  Figure 6. Therapeutic efficacy of tTF-NGR in a sarcoma xenograft model. (A) CD13-positive (CD13 +) staining of HT1080 fibrosarcoma cells as measured by flow cytometry (upper two panels). In the right histogram stained cells are depicted in red; unstained, in gray. Lower two panels, HTB 119 small cell lung cancer cells as negative control with 4.5% of the cells being CD13 positive. (B) Immunohistology of HT1080 xenografts showing intensity score 3 CD13 positivity (possibly overstained due to freezing and thawing). (C) Effect of systemically applied tTF-NGR on HT1080 fibrosarcoma growth in CD-1 nude mice. Tumor growth is significantly inhibited by six daily subcutaneous tTF-NGR injections (1 mg/kg bw; n = 6) compared to the saline control (n = 6); arrows indicate the time points of saline/tTF-NGR application. Data are presented as means with standard errors; asterisk denotes first day of statistical significance between tTF-NGR and saline on day 5 (t test, P ≤ .05).