惡性腫瘤轉(zhuǎn)移是腫瘤病人死亡的主要原因，也是當(dāng)今腫瘤研究領(lǐng)域的焦點(diǎn),。腫瘤轉(zhuǎn)移過程中,，瘤細(xì)胞首先脫離原發(fā)瘤，侵犯并穿過宿主基質(zhì)進(jìn)入循環(huán),，存活并到達(dá)遠(yuǎn)處毛細(xì)血管床,，在那里粘附并穿出血管，進(jìn)入器官實(shí)質(zhì),，增殖成繼發(fā)腫瘤,。
早在1889年，Paget即提出,，器官微環(huán)境（“土壤”）可影響特定腫瘤細(xì)胞（“種子”）的種植,、侵襲、存活,、生長,。腫瘤轉(zhuǎn)移早期常呈現(xiàn)特異臟器親合性，如結(jié)腸癌易轉(zhuǎn)移到肝臟,，肺癌易轉(zhuǎn)移到骨,、腎上腺和腦，前列腺癌易轉(zhuǎn)移到骨,。
Paget的“種子和土壤”假說指出,，癌癥轉(zhuǎn)移需要腫瘤細(xì)胞和周圍器官微環(huán)境之間相互作用。這些相互作用涉及到目前許多已知的生長因子受體和配體,。然而,，雖然調(diào)控原發(fā)性腫瘤生長的癌癥細(xì)胞信號(hào)通路得到了廣泛的研究，但腫瘤細(xì)胞與次級(jí)轉(zhuǎn)移灶器官之間相互作用的信號(hào)通路往往被忽視,。目前,，靶向治療已經(jīng)呈現(xiàn)出較好的臨床治療效果，但這只限于大多數(shù)原發(fā)腫瘤的治療,，很多轉(zhuǎn)移性癌癥仍無法得到完全治愈,。近日Cancer Metastasis Rev雜志上刊出了一則新研究，科學(xué)家重點(diǎn)討論了幾種生長因子信號(hào)通路在腫瘤只具有一般性轉(zhuǎn)移和特定轉(zhuǎn)移器官中的作用,，希望可以進(jìn)一步充分理解復(fù)雜的轉(zhuǎn)移過程,，最終能更好的治療轉(zhuǎn)移癌癥患者。（生物谷：Bioon.com)
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.
