Tumor cell-activated CARD9 signaling contributes tometastasis-associated macrophage polarization

M Yang., et al. Cell Death and Differentiation, 1290–1302 (2014)

Speaker: Dong-Jer Shiao (蕭東哲)                                   Time: 15:00~16:00, Oct. 1, 2014

Commentator: Dr. Pin ling (凌斌 老師)                  Place: Room 601

Abstract:

Earlier research has showed that tumor microenvironment containing immune cells infiltration mediates the tumor progression, drug resistance and ability of suppressing antitumor immune cells to sustain the tumor progression [1]. Metastasis-associated macrophage is considered to be a major component of tumor microenvironment. Metastasis-associated macrophage is a M2 phenotype macrophage that undergoes education within the tumor microenvironment. Nevertheless, the reformatting switching mechanisms of polarized macrophage to metastasis-associated macrophage by the tumor cell are yet to be determined. However NF-κB activation is an essential initiative for metastasis-associated macrophage polarization. Previous research in gastric B-cell lymphoma patients has demonstrated that B cells overexpressed caspase recruitment domain-containing protein 9 (CARD9) could presumably promote tumor cell proliferation via NF-κB activation [2]. In this current research authors would like to determine the role of CARD9 and its underlying signal pathway for metastasis-associated macrophage polarization. Authors have employedCARD9^-/- & wild type tumor-bearing mice to investigate tumor development. In result, tumor-infiltrated macrophages were able to express high levels of CARD9, which is essential for M2 macrophage polarization. Furthermore, results also showed that Syk activation is necessary for CARD9-BCL-MALT1 complex formation to activate NF-κB in the tumor microenvironment. In the conclusion, tumor secreting factors induced macrophage CARD9-BCL-MALT1 complex formation regulating M2 macrophage polarization which will support tumor metastasis. This could be a potential drug to target the tumor microenvironment improvising cancer drug therapy effect.

References

1.     Tlsty TD., et al. Tumor stroma and regulation of cancer development. Annual Review of Pathology Mechanisms of Disease. 2006;1:119-50.

2.     Nakamura S., et al.. Overexpression of caspase recruitment domain (CARD)

membrane-associated guanylate kinase 1 (CARMA1)andCARD9 in primary gastric B-cell lymphoma. Cancer. 2005;1:104(9):1885-93.