Quantitative Changes in Tumor-Associated M2 Macrophages Characterize Cholangiocarcinoma and their Association with Metastasis

Thanee, Malinee; Loilome, Watcharin; Techasen, Anchalee; Namwat, Nisana; Boonmars, Thidarut; Pairojkul, Chawalit; Yongvanit, Puangrat

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자료유형: 학술저널

저자정보: Thanee, Malinee (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) Loilome, Watcharin (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) Techasen, Anchalee (Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) Namwat, Nisana (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) Boonmars, Thidarut (Department of Parasitology, Faculty of Medicine, Khon Kaen University) Pairojkul, Chawalit (Department of Pathology, Faculty of Medicine, Khon Kaen University) Yongvanit, Puangrat (Department of Biochemistry, Faculty of Medicine, Khon Kaen University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제7호

발행연도: 2015.1

수록면: 3,043 - 3,050 (8page)

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The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

#Tumor-associated macrophages #cancer-associated fibroblasts #cholangiocarcinoma #metastasis

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