多效生长因子通过诱导肿瘤血管生成、重建肿瘤微环境和活化基质纤维发挥多功能肿瘤启动子作用

Pleiotrophin induced by tumor angiogenesis,tumor microenvironment and activation of reconstruction matrix fibers plays multifunctional tumor promoter

多效生长因子(pleiotrophin,PTN)是分泌型的肝素结合生长因子,具有136个氨基酸,在机体内广泛表达。它能通过特殊的信号通路,即跨膜蛋白酪氨酸磷酸酶(receptor protein tyrosine phosphataseβ/ζ,RPTPβ/ζ)受体转导信号。PTN也是原癌基因,它表达在人类肿瘤细胞中,并且来源于肿瘤的细胞链也会表达PTN。不论是不同细胞诱导产生的PTN还是PTN刺激的细胞,它们的相似之处都是高度恶性。此外,将PTN转化到细胞后能使潜在恶性细胞高度恶化。因此,在恶性细胞中PTN不适当的表达能作为肿瘤强有力的启动者。最近确认,在转基因小鼠模型中发现PTN能以乳腺癌病毒为靶向目标诱导乳腺癌更具有侵略性,在表型中更相似于硬癌。另外,PTN能显著增加肿瘤血管生成,重塑肿瘤微环境。

Pleiotrophin （PTN） is a widely expressed,regulated 136 amino acid secreted heparin-binding cytokine.It passes through a unique signaling pathway; the PTN receptor is the transmembrane receptor protein tyrosine phosphatase （RPTP） β/ζ.RPTPβ/ζ is inactivated by PTN,which leads to increase tyrosine phosphorylation of the downstream targets of the PTN/RPTPβ/ζ signaling pathway.The PTN gene also is a proto-oncogene; PTN is expressed in human tumor cells,and in cell lines derived from human tumors that express PTN.Importantly,properties of different cells induced by PTN in PTN-stimulated cells are strikingly similar to properties of highly malignant cells.Furthermore,transformed cells into which PTN is introduced undergo ‘ switches＇ to malignant cells of higher malignancy with properties that are strikingly similar to properties of PTN-stimulated cells.Thus,PTN signaling in malignant cells that inappropriately express PTN functions as a potent tumor promoter.Recently,in confirmation,PTN targeted by the mouse mammary tumor virus （MMTV） promoter in a transgenic mouse model was found to promote breast cancers to a more aggressive breast cancer cell phenotype that morphologically closely resembles scirrhous carcinoma in human; in addition,it promoted a striking increase in tumor angiogenesis and a remarkable degree of remodeling of the micro-environment.