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Significance of oral cancer‐associated fibroblasts in angiogenesis, lymphangiogenesis, and tumor invasion in oral squamous cell carcinoma
Author(s) -
Lin NanNan,
Wang Ping,
Zhao Dan,
Zhang FuJun,
Yang Kai,
Chen Rui
Publication year - 2017
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12452
Subject(s) - lymphangiogenesis , angiogenesis , lymphatic vessel , pathology , tumor progression , cancer , metastasis , immunohistochemistry , microvessel , medicine , lymphatic system , cancer cell , cancer research
Background Cancer‐associated fibroblasts ( CAF s) are recognized as a pivotal promoter in cancer initiation and development. However, the role of CAF s in the progression and metastasis of oral squamous cell carcinoma ( OSCC ) has not been fully elucidated. Materials and Methods Lymphatic vessel density ( LVD ) and microvessel density ( MVD ) and the expression of α‐smooth muscle actin (α‐ SMA ) and matrix metalloproteinase‐9 ( MMP ‐9) were evaluated by immunohistochemistry in 86 cases of OSCC . The correlations between α‐ SMA expression and MMP ‐9 expression, LVD , MVD , and other clinicopathological parameters were analyzed. In vitro invasion assay was performed to assess the effect of CAF s on the invasion of OSCC cells. We also investigated the effect of CAF s on the angiogenesis and lymphangiogenesis by inoculating CAF s with OSCC cells into nude mice subcutaneously. Results Positive expression of α‐ SMA protein was detected in 69.8% of the tumors. Increased α‐ SMA expression was correlated strongly with enhanced tumor invasion, higher tumor grade, increased risk of recurrence, lymph node involvement, and higher peritumoral lymphatic vessel density and microvessel density ( P < 0.05). CAF s induced more cancer cells to invade relative to normal fibroblasts ( NF s) ( P < 0.05). Compared with co‐injection of OSCC cells and NF s or injection of tumor cells alone, co‐injection of OSCC cells and CAF s resulted in earlier tumor formation and bigger tumor volume accompanied with increased angiogenesis and lymphangiogenesis ( P < 0.05). Conclusion CAF s may play critical roles in OSCC progression as an inducer of tumor invasion, angiogenesis, and lymphangiogenesis. Therapeutic strategies targeting CAF s against OSCC is promising and need further exploration.