癌细胞的转移是肿瘤的一种特殊本领，癌细胞能从原发部位沿着各种渠道到达身体的其他部位后继续生长，形成新的癌块，这种现象称为癌转移也叫癌扩散。要想治愈癌症，首先就要防止癌细胞的扩散。来自纪念斯隆－凯特琳癌症中心（Memorial Sloan Kettering Cancer Center）的研究人员获得了肿瘤相关巨噬细胞在促进恶性肿瘤扩增方面的新机制。这一研究成果公布在Genes & Development杂志上。
天然免疫细胞，包括巨噬细胞在内，都是肿瘤浸润细胞环境中的一个重要组成部分，即所谓的“肿瘤微环境”，肿瘤与其微环境之间存在动力学关联，能通过一些分泌因子调控细胞的生长和癌症的扩散。
在这篇文章中，研究人员Johanna Joyce等人发现了这种肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）是如何促进肿瘤生长和入侵的新机制，他们发现巨噬细胞能浸入胰腺，乳腺和肺部癌细胞中，高度表达蛋白酶cathepsin B和cathepsin S，从而导致肿瘤的生长和侵入。
而且有趣的是，研究人员还发现肿瘤本身还能促进cathepsin B和cathepsin S的活性增强，这主要是通过interleukin(IL)-4的介导作用。
这项研究为靶向肿瘤微环境的癌症治疗提供了新证据和新工具，靶向肿瘤微环境的癌症治疗也是目前扰乱癌症扩散扩增的一种重要方法。Joyce博士乐观的认为这种方法能选择性的靶向癌细胞通讯中的细胞，具有极大的治疗前景。（生物谷Bioon.com）
癌细胞转移影响因素：
Science：癌症转移可能比预想的早
Nature：与乳腺癌肿瘤形成和转移有关的两种miRNA
Cell：特殊细胞因子促使乳腺肿瘤转移
Nature Reviews Cancer：科学家提出癌症转移新解释
PNAS：非编码RNA可控制癌症转移
Cell Stem Cell：癌症干细胞控制肿瘤转移假说被证实
Cancer Research：苔虫内酯抗肿瘤转移作用机理
Nature：科学家发现阻断癌症转移的靶基因
PLoS ONE：巨噬细胞可帮助癌细胞转移
生物谷推荐原始出处：
Genes & Development January 15, 2010, doi:10.1101/gad.1874010
IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion
Vasilena Gocheva1, Hao-Wei Wang1, Bedrick B. Gadea, Tanaya Shree, Karen E. Hunter, Alfred L. Garfall, Tara Berman and Johanna A. Joyce2
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
Innate immune cells can constitute a substantial proportion of the cells within the tumor microenvironment and have been associated with tumor malignancy in patients and animal models of cancer; however, the mechanisms by which they modulate cancer progression are incompletely understood. Here, we show that high levels of cathepsin protease activity are induced in the majority of macrophages in the microenvironment of pancreatic islet cancers, mammary tumors, and lung metastases during malignant progression. We further show that tumor-associated macrophage (TAM)-supplied cathepsins B and S are critical for promoting pancreatic tumor growth, angiogenesis, and invasion in vivo, and markedly enhance the invasiveness of cancer cells in culture. Finally, we demonstrate that interleukin-4 (IL-4) is responsible for inducing cathepsin activity in macrophages in vitro and in vivo. Together, these data establish IL-4 as an important regulator, and cathepsin proteases as critical mediators, of the cancer-promoting functions of TAMs.
