| First Author | Ramani V | Year | 2018 |
| Journal | J Invest Dermatol | Volume | 138 |
| Issue | 11 | Pages | 2443-2451 |
| PubMed ID | 29857071 | Mgi Jnum | J:270919 |
| Mgi Id | MGI:6276509 | Doi | 10.1016/j.jid.2018.05.012 |
| Citation | Ramani V, et al. (2018) Melanoma-Derived Soluble DC-HIL/GPNMB Promotes Metastasis by Excluding T-Lymphocytes from the Pre-Metastatic Niches. J Invest Dermatol 138(11):2443-2451 |
| abstractText | Soluble factors from the primary tumor induce recruitment of bone marrow-derived progenitors to form tumor-supportive microenvironments or pre-metastatic niches in distal organs before metastasis. How tumor-secreted factors condition the sites for tumor progression remains ambiguous. B16 melanoma produces the secreted form of T cell-inhibitory DC-HIL (sDC-HIL) that travels to distal organs and potentiates the metastatic capacity of tumor cells. We studied the molecular mechanisms and found that sDC-HIL binds to select endothelial cells that co-localize with the sites where bone marrow-derived progenitors and tumor cells migrate. sDC-HIL-bound endothelial cells exist at a similar frequency in mice with or without tumors, and they are strongly associated with survival of intravenously injected tumor cells in the lung. sDC-HIL binding conferred T-cell suppressor function on the ECs and awakened the angiogenic property by inducing vascular endothelial growth factor expression, resulting in enhanced transendothelial migration of bone marrow-derived progenitors and tumor cells, but not for T cells. This selectivity is achieved by the T-cell binding of sDC-HIL, which prevents formation of the leading edges required for chemotaxis. Finally, inducing tumor expression of sDC-HIL significantly reduced tumor-infiltrated T cells. Therefore, the highly metastatic attribute of B16 melanoma can be explained by the endothelial gatekeeper function of sDC-HIL that limits lymphocyte transmigration to pre-metastatic niches. |
