American Association for Cancer Research
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Supplemental Figure S2 from MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell–Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages

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posted on 2023-03-30, 23:42 authored by Kazuya Yamada, Akihiko Uchiyama, Akihito Uehara, Buddhini Perera, Sachiko Ogino, Yoko Yokoyama, Yuko Takeuchi, Mark C. Udey, Osamu Ishikawa, Sei-ichiro Motegi

This file contains two supplementary figure S2. from Supplemental Figure S2: A. The amount of CD68+ macrophages in melanoma tumor in mice treated with clodronate liposomes or control liposomes. B. Survival in mice implanted with melanoma cells and MFG-E8 WT/KO MSC treated with clodoronate liposomes or control liposomes.


Japanese Dermatological Association

Takeda Science Foundation






Secretion of the powerful angiogenic factor MFG-E8 by pericytes can bypass the therapeutic effects of anti-VEGF therapy, but the mechanisms by which MFG-E8 acts are not fully understood. In this study, we investigated how this factor acts to promote the growth of melanomas that express it. We found that mouse bone marrow–derived mesenchymal stromal cells (MSC) expressed a substantial amount of MFG-E8. To assess its expression from this cell type, we implanted melanoma cells and MSC derived from wild type (WT) or MFG-E8 deficient [knockout (KO)] into mice and monitored tumor growth. Tumor growth and M2 macrophages were each attenuated in subjects coimplanted with KO-MSC compared with WT-MSC. In both xenograft tumors and clinical specimens of melanoma, we found that MFG-E8 expression was heightened near blood vessels where MSC could be found. Through in vitro assays, we confirmed that WT-MSC–conditioned medium was more potent at inducing M2 macrophage polarization, compared with KO-MSC–conditioned medium. VEGF and ET-1 expression in KO-MSC was significantly lower than in WT-MSC, correlating in vivo with reduced tumor growth and numbers of pericytes and M2 macrophages within tumors. Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283–92. ©2016 AACR.

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