华裔学者最新文章获得癌细胞扩散新发现

　　

来自澳大利亚新南威尔士大学（UNSW）医学院的科学家挑战一个传统观点：癌症转移是保护癌细胞的唯一途径。他们发现，癌细胞是与能让它们生长的“促生长”基质细胞一起从血液中迁移至机体其它部分的。这一研究有望为所有实体瘤以及其它具有最强侵略性的肿瘤制定有效的治疗策略。这篇文章发表在《American Journal of Pathology》杂志上。

领导这一研究的是UNSW胰腺癌研究小组主任Minoti Apte教授，文章的第一作者是华裔学者Zhihong Xu。

研究人员发现，源于原发肿瘤的“促生长”胰腺星状细胞（pancreatic stellate cell, PSC）可以侵入血管并随血流转移至远处部位，继而为癌细胞增殖生长建立良好的环境。研究人员在美国胰腺协会举办的年度科学会议上提出了他们的结果。

“人们总是认为癌症转移过程中，只有癌细胞发生移动。但我们首次表明，其实星状细胞是与癌细胞协同移动的。”Apte教授认为。“看起来，癌细胞在转移过程中携带了行李——星状细胞——这让癌细胞可以更快地在新地方扎根，并生活得更舒适。”

2008年，Apte等人发现PSC令胰腺肿瘤生长得更快更大，并导致更多的癌症转移发生。

而在最近的这次研究中，研究人员采用性别错配（gender mismatch）方法调查这些促生长细胞是否可以移动。雌性小鼠的胰腺中被注入雌性癌细胞和雄性PSC。7周后，所有小鼠的转移性结节都出现了Y染色体-阳性（雄性）细胞。

Apte说道：“这些Y染色体-阳性（雄性）细胞只能来自于雌性癌细胞以及雄性胰腺星状细胞。”现在我们面临的挑战就是要阻止PSC帮助并“教唆”胰腺癌细胞转移出原发肿瘤，还要防止或减少癌细胞在远处部位生长。

原文摘要：

Role of Pancreatic Stellate Cells in Pancreatic Cancer Metastasis.
Xu Z, Vonlaufen A, Phillips PA, Fiala-Beer E, Zhang X, Yang L, Biankin AV, Goldstein D, Pirola RC, Wilson JS, Apte MV.

From the Pancreatic Research Group,* South Western Sydney Clinical School and School of Medical Sciences; the Faculty of Medicine, The University of New South Wales; and the Garvan Institute of Medical Research, Sydney, Australia.

Abstract
Pancreatic stellate cells (PSCs) produce the stromal reaction in pancreatic cancer (PC), and their interaction with cancer cells facilitates cancer progression. This study investigated the role of human PSCs (hPSCs) in the metastatic process and tumor angiogenesis using both in vivo (orthotopic model) and in vitro (cultured PSC and PC cells) approaches. A gender mismatch study (injection of male hPSCs plus female PC cells into the pancreas of female mice) was conducted to determine whether hPSCs accompany cancer cells to metastatic sites. Metastatic nodules were examined by fluorescent in situ hybridization for the presence of the y chromosome. Angiogenesis was assessed by i) immunostaining tumors for CD31, an endothelial cell marker; and ii) quantifying human microvascular endothelial cell (HMEC-1) tube formation in vitro on exposure to conditioned media from hPSCs. Transendothelial migration was assessed in vitro by examining the movement of fluorescently labeled hPSCs through an endothelial cell monolayer. Human PSCs i) were found in multiple metastatic sites in each mouse injected with male hPSCs plus female PC cells; ii) increased CD31 expression in primary tumors from mice injected with MiaPaCa-2 and hPSCs and stimulated tube formation by HMEC-1 in vitro; and iii) exhibited transendothelial migration that was stimulated by cancer cells. Human PSCs accompany cancer cells to metastatic sites, stimulate angiogenesis, and are able to intravasate/extravasate to and from blood vessels.