Abstract
M2-polarized tumor associated macrophages (TAMs) play an important role in tumor progression. It has been reported that response gene to complement 32 (RGC-32) promotes M2 macrophage polarization. However, whether RGC-32 expression in macrophages could play a potential role in tumor progression remain unclear. Here we identified that increasing RGC-32 expression in colon cancer and tumor associated macrophages was positively correlated with cancer progression. In vitro studies confirmed that colon cancer cells upregulated RGC-32 expression of macrophages via secreting TGF-β1. RGC-32 expression promoted macrophage migration. In addition, stimulation of HCT-116 cells with the condition mediums of RGC-32-silienced or over-expressed macrophages affected tumor cell colony formation and migration via altered COX-2 expression. In an animal model, macrophages with RGC-32 knockdown significantly decreased the expression of COX-2 and Ki67 in the xenografts, and partly inhibited tumor growth. Together, our results provide the evidences for a critical role of TGF-β1/RGC-32 pathway in TAMs and colon cancer cells during tumor progression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Proliferation / genetics
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / mortality
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Colonic Neoplasms / pathology*
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Cyclooxygenase 2 / metabolism
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Disease Progression
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Female
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Humans
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Ki-67 Antigen / metabolism
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Macrophage Activation / drug effects
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Macrophage Activation / genetics*
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Macrophages / drug effects
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Macrophages / enzymology
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Macrophages / metabolism*
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Middle Aged
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Paracrine Communication
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Prognosis
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Transforming Growth Factor beta1 / metabolism
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Transforming Growth Factor beta1 / pharmacology
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / genetics*
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD68 antigen, human
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Cell Cycle Proteins
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Ki-67 Antigen
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MKI67 protein, human
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Muscle Proteins
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Nerve Tissue Proteins
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RGCC protein, human
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Transforming Growth Factor beta1
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Cyclooxygenase 2