Role and clinicopathological significance of platelets on tumor angiogenesis

当癌细胞与血小板共孵育时，癌细胞产生的IL-8比没有血小板孵育的癌细胞产生的IL-8增加。白细胞介素-8 mRNA在癌细胞中的表达也因血小板的存在而增强。在化学侵袭实验中，血小板促进胰腺癌细胞的侵袭性。Geratin Zymography和Western blot分析显示，血小板显著增强了癌细胞的MMP-9。这些对MMP-9产生的促进作用被抗血小板药物的加入所抑制。此外，通过三维培养和成管实验评估血小板对肿瘤血管生成的影响。与单独培养癌细胞的上清相比，与癌细胞和血小板共培养的上清可促进HUVEC的管状形成。当血小板和癌细胞共孵育时，VEGF的产生协同增加。这些发现表明，血小板促进肿瘤血管生成和侵袭性，部分是通过促进癌细胞血管生成因子和金属蛋白酶的产生。

When cancer cells were co-incubated with platelets, IL-8 production by cancer cells was increased compared with IL-8 production by cancer cells incubated without platelets. The expression of IL-8 mRNA by cancer cells was also found to be enhanced by the existence of platelets from Northern blot analysis. Platelets promoted the invasiveness of pancreatic cancer cells in the chemoinvasion assay. Geratin Zymography and Western blot analysis revealed that MMP-9 from cancer cells was significantly enhanced by platelets. These promotive effects on MMP-9 production were inhibited by the addition of anti-platelet agents. Furthermore, the effects of platelets on tumor angiogenesis were evaluated by 3D cultivation and tube formation assay. Tube formation of HUVEC was promoted by the supernatant from co-culture with cancer cells and platelets, compared with the supernatant from cancer cells alone. The production of VEGF was synergistically increased when platelets and cancer cells were co-incubated. These findings suggest that platelets enhanced tumor angiogenesis and invasiveness, partly, by enhancement of cancer cells on the production of both angiogenic factors and metalloprotease.