Transforming Growth Factor-β in Lung Cancer, Carcinogenesis, and Metastasis

Abstract

Transforming growth factor-beta (TGF-β) is a multifunctional regulatory polypeptide that is the prototypical member of a large family of cytokines that controls many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. Contrary to the initial concept that these proteins may be down-regulated in cancer cells to promote their growth, a marked increase in the expression of TGF-β has often been found in human cancers in vivo, including cancer of the lung. Moreover, in lung cancer, increased expression of TGF-β correlates with more advanced stages of malignancy and metastasis and with decreased survival. Increased expression of TGF-β is usually accompanied by a loss in the growth inhibitory response to TGF-β. Indeed, some lung cancer cells in culture demonstrate a progressive loss of the growth inhibitory response to TGF-β that varies directly with the malignant stage of the original tumor. The study of the molecular events associated with the escape of cancer cells from growth regulation by TGF-β has provided insight into mechanisms underlying carcinogenesis. Specific defects in TGF-β receptors, TGF-β-related signal transduction/gene activation, and TGF-β-regulated cell cycle proteins, have been implicated in the oncogenesis of human lung cancer and metastasis. This review provides background information on TGF-β and updates the status of our knowledge of the role of TGF-β in lung cancer, carcinogenesis, and metastasis.