Lee C, Sintich S M, Mathews E P, Shah A H, Kundu S D, Perry K T, Cho J S, Ilio K Y, Cronauer M V, Janulis L, Sensibar J A
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Prostate. 1999 Jun 1;39(4):285-90. doi: 10.1002/(sici)1097-0045(19990601)39:4<285::aid-pros9>3.0.co;2-7.
The present review summarizes the cellular action of TGF-beta in benign and malignant growth of the prostate.
TGF-beta is a pleiotropic growth factor. It plays an important role in the regulation of growth and differentiation in many cells. In benign prostatic epithelia, its action is mediated through a paracrine mechanism. It inhibits proliferation and induces apoptosis in prostatic epithelia. It provides a mechanism to maintain epithelial homeostasis in the prostate. In prostatic stroma, its continual action leads to smooth muscle differentiation. This effect of TGF-beta may regulate the development of prostatic smooth muscle nodules in benign prostatic hyperplasia.
As prostatic epithelial cells undergo malignant transformation, two major events occur regarding TGF-beta action. These include the loss of expression of functional TGF-beta receptors and overproduction of TGF-beta in malignant cells. The loss of expression of functional TGF-beta receptors provides a growth advantage to cancer cells over their benign counterparts. The overproduction of TGF-beta by cancer cells has a multitude of adverse consequences. TGF-beta can promote extracellular matrix production, induce angiogenesis, and inhibit host immune function. The biological consequence of these activities is an enhanced tumorigenicity in prostate cancer. Results of our recent studies with a rat prostate cancer model suggest that the immunosuppressive effect of TGF-beta seems to be the primary cause of tumor progression. This is because, if these cancer cells were engineered to reduce the production of TGF-beta, tumor growth was inhibited in syngeneic hosts but not in immune compromised hosts.
Our future research should take advantage of this knowledge to devise therapeutic strategies aimed at eradicating prostate cancer.
本综述总结了转化生长因子-β（TGF-β）在前列腺良性和恶性生长中的细胞作用。
TGF-β是一种多效性生长因子。它在许多细胞的生长和分化调节中起重要作用。在良性前列腺上皮中，其作用通过旁分泌机制介导。它抑制前列腺上皮细胞增殖并诱导其凋亡。它为维持前列腺上皮稳态提供了一种机制。在前列腺基质中，其持续作用导致平滑肌分化。TGF-β的这种作用可能调节良性前列腺增生中前列腺平滑肌结节的形成。
随着前列腺上皮细胞发生恶性转化，TGF-β的作用出现两个主要变化。这些变化包括功能性TGF-β受体表达缺失以及恶性细胞中TGF-β的过量产生。功能性TGF-β受体表达缺失使癌细胞比其良性对应细胞具有生长优势。癌细胞中TGF-β的过量产生会产生多种不良后果。TGF-β可促进细胞外基质产生、诱导血管生成并抑制宿主免疫功能。这些活动的生物学后果是前列腺癌的致瘤性增强。我们最近用大鼠前列腺癌模型进行的研究结果表明，TGF-β的免疫抑制作用似乎是肿瘤进展的主要原因。这是因为，如果对这些癌细胞进行改造以减少TGF-β的产生，在同基因宿主中肿瘤生长受到抑制，但在免疫受损宿主中则不然。
我们未来的研究应利用这些知识来设计旨在根除前列腺癌的治疗策略。
