Proceedings of the National Academy of Sciences of the United States of America · 2023
MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Maji Santanu, Pradhan Anjan K, Kumar Amit, Bhoopathi Praveen, Mannangatti Padmanabhan, Guo Chunqing, Windle Jolene J, Subler Mark A, Wang Xiang-Yang, Semmes Oliver J, Nyalwidhe Julius O, Mukhopadhyay Nitai, Paul Asit Kr, Hatfield Bryce, Levit Michael M, Madan Esha, Sarkar Devanand, Emdad Luni, Cohen David J, Gogna Rajan, Cavenee Webster K, Das Swadesh K, Fisher Paul B
Аннотация
Bone metastasis is a frequent and incurable consequence of advanced prostate cancer (PC). An interplay between disseminated tumor cells and heterogeneous bone resident cells in the metastatic niche initiates this process. Melanoma differentiation associated gene-9 (mda-9/Syntenin/syndecan binding protein) is a prometastatic gene expressed in multiple organs, including bone marrow-derived mesenchymal stromal cells (BM-MSCs), under both physiological and pathological conditions. We demonstrate that PDGF-AA secreted by tumor cells induces CXCL5 expression in BM-MSCs by suppressing MDA-9-dependent YAP/MST signaling. CXCL5-derived tumor cell proliferation and immune suppression are consequences of the MDA-9/CXCL5 signaling axis, promoting PC disease progression. mda-9 knockout tumor cells express less PDGF-AA and do not develop bone metastases. Our data document a previously undefined role of MDA-9/Syntenin in the tumor and microenvironment in regulating PC bone metastasis. This study provides a framework for translational strategies to ameliorate health complications and morbidity associated with advanced PC.