Interleukin-30 promotes breast cancer growth and progression
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels l'interleukine 30 favorise la croissance et la progression d'une tumeur de cancer du sein triplement négatif
The inflammatory tissue microenvironment which promotes the development of breast cancer (BRCA) is not fully understood. Here we report a role for elevated IL-30 in supporting the BRCA cell viability and invasive migration. IL-30 was absent in normal mammary ducts, ductules and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, its IL-30 was expressed frequently in BRCA specimens where it was associated with triple-negative and HER2+ molecular subtypes. In stromal leukocytes found in primary tumors or tumor-draining lymph nodes, which included mainly CD14+ monocytes, CD68+ macrophages and CD33+/CD11b+ myeloid cells, IL-30 levels increased with disease stage and correlated with recurrence. A negative correlation was determined between IL-30 expression by nodal stromal leukocytes and overall survival. In vitro studies showed that human recombinant IL-30 upregulated expression of a pro-oncogenic program, including especially IL-6 in both triple-negative and HER2+ BRCA cells. In triple-negative BRCA cells, IL-30 boosted a broader program of proliferation, invasive migration and an inflammatory milieu associated with KISS1-dependent metastasis. Silencing of STAT1/STAT3 signaling hindered the regulation of the primary growth and progression factors in BRCA cells. IL-30 administration in vivo fostered the growth of triple-negative BRCA by promoting proliferation and vascular dissemination of cancer cells and the accumulation of intratumoral CD11b+/Gr1+myeloid cell infiltrates. Overall, our results show how IL-30 regulates BRCA cell viability, migration and gene expression to promote BRCA growth and progression and its impact on patient outcome.
Cancer Research , article en libre accès, 2015