Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer
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Journal of Translational Medicine Open Access
RESEARCH
Tumor‑associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non‑small cell lung cancer patients Ilseon Hwang1,7, Jeong Won Kim1,8, Kris Ylaya1, Eun Joo Chung2, Haruhisa Kitano3,5, Candice Perry4, Jun Hanaoka5, Junya Fukuoka6, Joon‑Yong Chung1* and Stephen M. Hewitt1*
Abstract Background: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally char‑ acterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC). Methods: Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system. Results: CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p
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