Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

摘要: Cancer development and progression to metastasis is a complex process, which largely depends on bidirectional communication between tumor cells their microenvironment. Melanoma differentiation associated gene-9 (mda-9, also known as Syntenin-1, SDCBP), gene first cloned by our group, robustly expressed in multiple cancers including melanoma contributes invasion cell-intrinsic manner. However, the role of MDA-9/Syntenin cell-extrinsic microenvironment remains unclear even though ubiquitously most organs that are active metastatic sites for melanoma, e.g., lung, lymph node, brain, liver. In this study, we explored effect environmental mda-9/syntenin expression growth using immunocompetent animal models, syngeneic B16 xenograft intravenous mouse model genetically engineered (GEM) melanoma. Host-deficient mice negatively impacted subcutaneously implanted lung metastasis. Absence suppressed modulating situ Interleukin 17A (IL17A) impaired recruitment myeloid derived suppressor (MDSCs) Th17 compared wild type animals. Additionally, loss spontaneous (melanocyte-specific pten BrafV600E mutation) significantly delayed initiation nodes lungs. The present study highlights novel tumor-promoting inflammation immune suppression. These observations along with other documented roles cancer support potential relevance carcinogenic process target developing improved therapies either genetic or pharmacologic approaches treat prevent cancers.