Interleukin-30 promotes breast cancer growth and progression

Irma Airoldi, Claudia Cocco, Carlo Sorrentino, Domenico Angelucci, Serena Di Meo, Lamberto Manzoli, Silvia Esposito, Domenico Ribatti, Maria Bertolotto, Laura Iezzi, Clara Natoli, Emma Di Carlo

Research output: Contribution to journalArticle

Abstract

The inflammatory tissue microenvironment that promotes the development of breast cancer is not fully understood. Here we report a role for elevated IL30 in supporting the breast cancer cell viability and invasive migration. IL30 was absent in normal mammary ducts, ductules, and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, IL30 was expressed frequently in breast cancer 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, IL30 levels increased with disease stage and correlated with recurrence. A negative correlation was determined between IL30 expression by nodal stromal leukocytes and overall survival. In vitro studies showed that human recombinant IL30 upregulated expression of a prooncogenic program, including especially IL6 in both triplenegative and HER2+ breast cancer cells. In triple-negative breast cancer cells, IL30 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 breast cancer cells. IL30 administration in vivo fostered the growth of triple-negative breast cancer by promoting proliferation and vascular dissemination of cancer cells and the accumulation of intratumoral CD11b+/Gr1+ myeloid cell infiltrates. Overall, our results show how IL30 regulates breast cancer cell viability, migration, and gene expression to promote breast cancer growth and progression and its impact on patient outcome.

Original languageEnglish
Pages (from-to)6218-6229
Number of pages12
JournalCancer Research
Volume76
Issue number21
DOIs
Publication statusPublished - Nov 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Airoldi, I., Cocco, C., Sorrentino, C., Angelucci, D., Di Meo, S., Manzoli, L., Esposito, S., Ribatti, D., Bertolotto, M., Iezzi, L., Natoli, C., & Di Carlo, E. (2016). Interleukin-30 promotes breast cancer growth and progression. Cancer Research, 76(21), 6218-6229. https://doi.org/10.1158/0008-5472.CAN-16-0189