What question did this study set out to answer?

To investigate whether breast cancer cells shed sphingosine 1-phosphate receptor 2 via exosomes and determine how recipient fibroblasts process this receptor to alter cellular signaling.

June 29, 2018OncotargetOpen Access

The sphingosine 1-phosphate receptor 2 is shed in exosomes from breast cancer cells and is N-terminally processed to a short constitutively active form that promotes extracellular signal regulated kinase activation and DNA synthesis in fibroblasts

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To investigate whether breast cancer cells shed sphingosine 1-phosphate receptor 2 via exosomes and determine how recipient fibroblasts process this receptor to alter cellular signaling.
Purified HSP70-positive and CD63-positive exosomes released by MDA-MB-231 breast cancer cells and tracked uptake in cultured fibroblasts.
Engineered an N-terminally truncated S1P2 receptor construct and expressed it in HEK293 cells to assess constitutive signaling capacity.
Modeled S1P2 activation and G protein engagement using the published crystal structure of the homologous S1P1 receptor.
Breast cancer cells shed full-length S1P2 (40 kDa) within exosomes, which fibroblasts internalize and cleave into a shortened, constitutively active 36-kDa form.
The truncated receptor stimulates extracellular signal-regulated kinase-1/2 (ERK-1/2) signaling and promotes DNA synthesis in recipient fibroblasts.
Structural modeling indicates that N-terminal cleavage relieves transmembrane helix tension between TM1 and TM7, facilitating the TM6-TM7 separation necessary for G protein coupling.

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Implication

Experimental study reveals exosomal S1P2 receptor transfer and truncation in fibroblasts, indicating a mechanism for cancer-driven microenvironment remodeling.

Cite This Study

Buri et al. (2018) studied this question.

synapsesocial.com/papers/6ab35dbe4ddda921142bc78f https://doi.org/10.18632/oncotarget.25658

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Implication

Experimental study reveals exosomal S1P2 receptor transfer and truncation in fibroblasts, indicating a mechanism for cancer-driven microenvironment remodeling.

The sphingosine 1-phosphate receptor 2 is shed in exosomes from breast cancer cells and is N-terminally processed to a short constitutively active form that promotes extracellular signal regulated kinase activation and DNA synthesis in fibroblasts

Key Points

Discussion

Implication

Cite This Study

The sphingosine 1-phosphate receptor 2 is shed in exosomes from breast cancer cells and is N-terminally processed to a short constitutively active form that promotes extracellular signal regulated kinase activation and DNA synthesis in fibroblasts

Key Points

Discussion

Implication

Cite This Study

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