Van Laethem J L, Resibois A, Adler M, Peny M O, Ohtani H, Robberecht P
Department of Gastroenterology and Hepatopancreatology, Erasme Hospital, Université Libre de Bruxelles, Belgium.
Dig Dis Sci. 1996 Sep;41(9):1741-8. doi: 10.1007/BF02088739.
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine and is thought to be involved in colorectal tumorigenesis as a regulator of cell growth and differentiation. This role is mainly supported by in vitro studies while its role in vivo remains unclear. The aim of the present study was to investigate whether the TGF-beta 1 precursor (beta 1-LAP) and the latent TGF-beta 1 binding protein (LTBP) are expressed in colorectal adenomas, the presumed precursors of most of colorectal adenocarcinomas. TGF-beta 1 precursor and LTBP were examined in 35 adenomas and 10 normal colonic mucosa specimens by immunohistochemistry, using specific polyclonal antibodies. In normal colonic mucosa, beta 1-LAP was moderately expressed in epithelial crypt cells and in the stromal cells in the lamina propria. In adenomas, beta 1-LAP was localized in epithelial cells with an heterogeneous pattern and was also present in stromal cells around the adenomatous glands. LTBP was not detected in epithelial cells but was observed in stromal cells and in the extracellular matrix (ECM). beta 1-LAP expression in epithelial cells did not correlate with the grade of dysplasia, while LTBP localized in stromal cells and ECM appeared to be closely associated with areas of higher grade of dysplasia. This study is the first demonstration of both beta 1-LAP and LTBP in colorectal adenomas with different dysplasia grades. Our results suggest that TGF-beta 1 might be involved in the mechanisms controlling in vivo colorectal tumorigenesis and support a role for the stromal-associated TGF-beta 1.
转化生长因子-β1（TGF-β1）是一种多功能细胞因子，被认为作为细胞生长和分化的调节因子参与结直肠癌的发生。这一作用主要得到体外研究的支持，而其在体内的作用仍不清楚。本研究的目的是调查TGF-β1前体（β1-LAP）和潜伏性TGF-β1结合蛋白（LTBP）是否在结直肠腺瘤中表达，结直肠腺瘤是大多数结直肠癌的推测前体。通过免疫组织化学，使用特异性多克隆抗体，在35例腺瘤和10例正常结肠黏膜标本中检测TGF-β1前体和LTBP。在正常结肠黏膜中，β1-LAP在上皮隐窝细胞和固有层的基质细胞中中度表达。在腺瘤中，β1-LAP以异质性模式定位于上皮细胞，也存在于腺瘤性腺体周围的基质细胞中。上皮细胞中未检测到LTBP，但在基质细胞和细胞外基质（ECM）中观察到。上皮细胞中β1-LAP的表达与发育异常程度无关，而定位于基质细胞和ECM中的LTBP似乎与发育异常程度较高的区域密切相关。本研究首次在不同发育异常等级的结直肠腺瘤中证实了β1-LAP和LTBP的存在。我们的结果表明，TGF-β1可能参与体内控制结直肠癌发生的机制，并支持基质相关TGF-β1的作用。
