Cancer Metast Rev：生长因子对肿瘤转移的作用

恶性肿瘤转移是肿瘤病人死亡的主要原因，也是当今肿瘤研究领域的焦点。肿瘤转移过程中，瘤细胞首先脱离原发瘤，侵犯并穿过宿主基质进入循环，存活并到达远处毛细血管床，在那里粘附并穿出血管，进入器官实质，增殖成继发肿瘤。

早在1889年，Paget即提出，器官微环境（“土壤”）可影响特定肿瘤细胞（“种子”）的种植、侵袭、存活、生长。肿瘤转移早期常呈现特异脏器亲合性，如结肠癌易转移到肝脏，肺癌易转移到骨、肾上腺和脑，前列腺癌易转移到骨。

Paget的“种子和土壤”假说指出，癌症转移需要肿瘤细胞和周围器官微环境之间相互作用。这些相互作用涉及到目前许多已知的生长因子受体和配体。然而，虽然调控原发性肿瘤生长的癌症细胞信号通路得到了广泛的研究，但肿瘤细胞与次级转移灶器官之间相互作用的信号通路往往被忽视。目前，靶向治疗已经呈现出较好的临床治疗效果，但这只限于大多数原发肿瘤的治疗，很多转移性癌症仍无法得到完全治愈。近日Cancer Metastasis Rev杂志上刊出了一则新研究，科学家重点讨论了几种生长因子信号通路在肿瘤只具有一般性转移和特定转移器官中的作用，希望可以进一步充分理解复杂的转移过程，最终能更好的治疗转移癌症患者。

doi:10.1007/s10555-012-9380-x
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Growth factor signaling in metastasis: current understanding and future opportunities

Frank J. Lowery and Dihua Yu

Paget’s “seed and soil” hypothesis stated that cancer metastasis requires permissive interactions between tumor cells and secondary organ microenvironments. Many of these “permissive interactions” are now known to be growth factor receptor and ligand interactions by which metastatic tumor cells coopt signaling pathways normally used by host organs. However, although cancer cell signaling pathways responsible for primary cancer growth have been extensively characterized, signaling pathways important in supporting tumor cell–secondary organ heterotypic interactions have been neglected. Even as targeted therapies have shown promise and efficacy in treating myriad primary tumors, metastatic cancer remains incurable. Here, we will discuss several growth factor signaling pathways known to be involved in both general and site-specific metastasis. We will address the complexity in generalizing the role of growth factor signaling in metastasis, as both pro- and antimetastatic roles for the same pathways have been demonstrated depending upon context. We will discuss the limitations of current usage of targeted therapies to pathways known to be dysregulated in metastasis. We propose that the future of cancer metastasis-targeted therapy will lie in better understanding of the interactions between tumor cells and the secondary organ microenvironments that may guide rationally designed personalized combinatorial targeted regimens. We hope to promote research to better understand the complex process of metastasis and ultimately better treatments for the abjectly underserved population of patients with metastatic cancer.