Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes.

Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes. Oncotarget. 2019 Mar 15;10(22):2212-2223 Authors: Yagnik G, Rutowski MJ, Shah SS, Aghi MK Abstract Tumor-associated macrophages (TAMs) polarize to M1 and M2 subtypes exerting anti-tumoral and pro-tumoral effects, respectively. To date, little is known about TAMs, their subtypes, and their roles in non-functional pituitary adenomas (NFPAs). We performed flow cytometry on single cell suspensions from 16 NFPAs, revealing that CD11b+ myeloid cells comprise an average of 7.3% of cells in NFPAs (range = 0.5%-27.1%), with qPCR revealing most CD11b+ cells to be monocyte-derived TAMs rather than native microglia. The most CD11b-enriched NFPAs (10-27% CD11b+) were the most expansile (size>3.5 cm or MIB1>3%). Increasing CD11b+ fraction was associated with decreased M2 TAMs and increased M1 TAMs. All NFPAs with cavernous sinus invasion had M2/M1 gene expression ratios above one, while 80% of NFPAs without cavernous sinus invasion had M2/M1<1 (P = 0.02). Cultured M2 macrophages promoted greater invasion (P < 10-5) and proliferation (P = 0.03) of primary NFPA cultures than M1 macrophages in a manner inhibited by siRNA targeting S100A9 and EZH2, respectively. Primary NFPA cultures were of two types: some recruited more monocytes in an MCP-1-dependent manner and polarized these to M2 TAMs, while others recruited fewer monocytes and polarize...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research