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. 2012 Dec 17;123(1):189–205. doi: 10.1172/JCI64993

Figure 13. Bidirectional signaling between BCCs and MSCs.

Figure 13

Hypoxia induces recruitment of bone marrow–derived MSCs to the primary tumor site. MSC-BCC interaction induces CXCL10, CCL5, and VEGFR1 expression in MSCs and CXCR3, CCR5, and PGF expression in BCCs. MSC→BCC interaction is mediated by CCL5→CCR5 and CXCL10→CXCR3 signaling. BCC→MSC interaction is mediated by PGF→VEGFR1 signaling, which induces CXCL10 expression in MSCs and thereby establishes a positive feedback loop between the 2 cell types. The PGF→VEGFR1 interaction is important for MSC homing, and CXCL10→CXCR3 and CCL5→CCR5 signaling promote BCC metastasis. The consequence of these interactions is the expression of genes that enhance invasion and the metastasis of BCCs to the lungs and LNs. The expression of CXCR3 and PGF (and probably CCR5) in BCCs as well as VEGFR1 (and perhaps CXCL10 and CCL5) in MSCs are regulated by HIFs.