转化生长因子-β在上皮恶性肿瘤中的作用及其与口腔癌发病机制的相关性（第二部分）

The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II).

作者信息

Prime S S, Davies M, Pring M, Paterson I C

机构信息

Department of Oral and Dental Science, Division of Oral Medicine, Pathology and Microbiology, Bristol Dental Hospital and School, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom.

出版信息

Crit Rev Oral Biol Med. 2004 Nov 1;15(6):337-47. doi: 10.1177/154411130401500603.

DOI:10.1177/154411130401500603

PMID:15574678

Abstract

The role of transforming growth factor-beta (TGF-beta) in epithelial malignancy is complex, but it is becoming clear that, in the early stages of carcinogenesis, the protein acts as a potent tumor suppressor, while later, TGF-beta can function to advance tumor progression. We review the evidence to show that the pro-oncogenic functions of TGF-beta are associated with (1) a partial loss of response to the ligand, (2) defects of components of the TGF-beta signal transduction pathway, (3) over-expression and/or activation of the latent complex, (4) epithelial-mesenchymal transition, and (5) recruitment of signaling pathways which act in concert with TGF-beta to facilitate the metastatic phenotype. These changes are viewed in the context of what is known about the pathogenesis of oral cancer and whether this knowledge can be translated into the development of new therapeutic modalities.

摘要

转化生长因子-β（TGF-β）在上皮恶性肿瘤中的作用较为复杂，但越来越清楚的是，在致癌作用的早期阶段，该蛋白作为一种有效的肿瘤抑制因子发挥作用，而在后期，TGF-β可促进肿瘤进展。我们综述相关证据以表明，TGF-β的促癌功能与以下因素有关：（1）对配体的反应部分丧失；（2）TGF-β信号转导途径成分的缺陷；（3）潜伏复合物的过度表达和/或激活；（4）上皮-间质转化；（5）募集与TGF-β协同作用以促进转移表型的信号通路。我们从已知的口腔癌发病机制的角度审视这些变化，以及这些知识是否能够转化为新治疗方法的开发。