Conditioned media from M1 but not M2 macrophage phenotype inhibits proliferation of thr colon cancer cell lines HT29 and CACO-2

• BackgroundTumor associated macrophages (TAMs) are often present at a high level in colorectal cancer (CRC) but whether the presence of TAMs in CRC is good or bad is unclear. Macrophages can be categorized into two main subgroups, M1 or M2, that display pro – and anti-inflammatory properties respectively. An improved knowledge of the different macrophage phenotypes will broaden the understanding of their involvement in CRC. We have used an in vitro model to study the effects of human M1 and M2 macrophages on the growth and cell cycle of colon cancer cell lines. MethodHuman monocytes were differentiated into M1 or M2 macrophages and conditioned media was collected. Effects of the conditioned media were measured on the colon cancer cell lines HT-29 and CACO-2 in regards to proliferation, cell cycle distribution and apoptosis. A protein array was used to analyze the released amount of 42 different cytokines from M1 and M2 macrophages into the collected conditioned media. ResultsGrowth arrest was induced in HT-29 and CACO-2 by M1 conditioned media, while M2 conditioned media had no major effect. Analysis of cell cycle distribution and apoptosis in HT-29 cells revealed that treatment with M1 conditioned media on these cells increased apoptosis and caused a disturbed cell cycle with accumulation in G0/G1 and G2/M and a corresponding reduction in S-phase. The protein array revealed several cytokines expressed in M1 with potential inhibitory growth effects. We treated HT-29 cells with two of the candidates, TNF-a and CXCL9, but neither induced growth arrest. ConclusionM1 – but not M2-macrophages had a major inhibitory effect on the growth of the colon cancer cell lines HT-29 and CACO-2 and suggest a role for M1 macrophages in anti-tumor activity and possible favorable outcome for CRC patients.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)

Keyword

Biomedical Sciences

Biomedicinsk vetenskap

Publication and Content Type

ref (subject category)

kon (subject category)