成纖維細(xì)胞生長因子受體（FGFR）對腫瘤的生長和癌癥病人的生存起著至關(guān)重要的作用。相比于其他受體酪氨酸激酶,，科學(xué)家也一直將成纖維細(xì)胞生長因子（成纖維細(xì)胞生長因子）作為一種治療癌癥的靶標(biāo)來開展研究,。
近日,，研究發(fā)現(xiàn)FGFR信號(hào)抑制后對原位乳腺66c14癌模型腫瘤生長、轉(zhuǎn)移和淋巴血管形成的影響,。體外研究表明FGFR抑制后,，66c14細(xì)胞增殖比對照組慢。小鼠植入FGFR表達(dá)抑制的腫瘤細(xì)胞后,，66c14腫瘤的生長和肺轉(zhuǎn)移灶減少,，同時(shí)有更好的整體生存率。
FGFR表達(dá)缺失的腫瘤細(xì)胞VEGFR-3（血管內(nèi)皮生長因子受體3）以及VEGF-C（血管內(nèi)皮生長因子c）mRNA的表達(dá)也減少,。這些數(shù)據(jù)證實(shí)成纖維細(xì)胞生長因子和血管內(nèi)皮生長因子對于血管形成是必須的,，針對FGFR信號(hào)可能是一個(gè)非常有前景的抑制腫瘤淋巴管轉(zhuǎn)移和擴(kuò)散的方法。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0039540
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Blocking Fibroblast Growth Factor Receptor Signaling Inhibits Tumor Growth, Lymphangiogenesis, and Metastasis
Frédéric Larrieu-Lahargue, Alana L. Welm, Marion Bouchecareilh, Kari Alitalo, Dean Y. Li, Andreas Bikfalvi*, Patrick Auguste
Fibroblast Growth Factor receptor (FGFR) activity plays crucial roles in tumor growth and patient survival. However, FGF (Fibroblast Growth Factor) signaling as a target for cancer therapy has been under-investigated compared to other receptor tyrosine kinases. Here, we studied the effect of FGFR signaling inhibition on tumor growth, metastasis and lymphangiogenesis by expressing a dominant negative FGFR (FGFR-2DN) in an orthotopic mouse mammary 66c14 carcinoma model. We show that FGFR-2DN-expressing 66c14 cells proliferate in vitro slower than controls. 66c14 tumor outgrowth and lung metastatic foci are reduced in mice implanted with FGFR-2DN-expressing cells, which also exhibited better overall survival. We found 66c14 cells in the lumen of tumor lymphatic vessels and in lymph nodes. FGFR-2DN-expressing tumors exhibited a decrease in VEGFR-3 (Vascular Endothelial Growth Factor Receptor-3) or podoplanin-positive lymphatic vessels, an increase in isolated intratumoral lymphatic endothelial cells and a reduction in VEGF-C (Vascular Endothelial Growth Factor-C) mRNA expression. FGFs may act in an autocrine manner as the inhibition of FGFR signaling in tumor cells suppresses VEGF-C expression in a COX-2 (cyclooxygenase-2) or HIF1-α (hypoxia-inducible factor-1 α) independent manner. FGFs may also act in a paracrine manner on tumor lymphatics by inducing expression of pro-lymphangiogenic molecules such as VEGFR-3, integrin α9, prox1 and netrin-1. Finally, in vitro lymphangiogenesis is impeded in the presence of FGFR-2DN 66c14 cells. These data confirm that both FGF and VEGF signaling are necessary for the maintenance of vascular morphogenesis and provide evidence that targeting FGFR signaling may be an interesting approach to inhibit tumor lymphangiogenesis and metastatic spread.
