Aberrant TGF-beta Production and Regulation in Metastatic Malignancy

被引：61

作者：

Schwarz, Lois C. ^{[1
]}

Wright, Jim A. ^{[1
]}

Gingras, Marie-Claude ^{[1
]}

Kondaiah, Paturu ^{[2
]}

Danielpour, David ^{[2
]}

Pimentel, Mark ^{[1
]}

Sporn, Michael B. ^{[2
]}

Greenberg, Arnold H. ^{[1
]}

机构：

[1] Manitoba Inst Cell Biol, 100 Olivia St, Winnipeg, MB R3E OV9, Canada

[2] NCI, Lab Chemoprevent, NIH, Bethesda, MD 20892 USA

来源：

GROWTH FACTORS | 1990年 / 3卷 / 02期

关键词：

TGF-beta secretion; regulation; malignancy;

D O I：

10.3109/08977199009108274

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We haw examined the possible role of transforming growth factor-beta (TGF-beta) in metastatic malignancy by analyhg the production and activation of TGF-beta(1) and -beta(2), and the regulation of TGF-beta-responsive genes in oncogene-transformed metastatic fibrosarcomas. All transformed lines derived from either 10T1/2 or NIH 3T3 by either H-ras or protein-kinasc encoding oncogenes produced more TCF-beta than parental cells. However, only highly metastatic fibro-sarcomas secreted activated TGF-beta at rates that were greater than parental fibroblasts. Immunohistochemical staining for TGF-beta(1) showed widespread intra- and extracellular distribution in metastatic lung nodules and adjacent tissue. Cells isolated from tumors successfully metastasizing to the lung had TGF-beta(1), mRNA levels which were increased 19-fold over in vitro controls. Despite the greatly enhanced rate of secretion of activated TGF-beta, metastatic cells exhibited markedly altered responses of TGF-beta(1), and TGF-beta(2), being unable to either increase collagen secretion or enhance collagen alpha 2(1) or TGF-beta(1) mRNA levels. This lack of response was not due to either altered TGF-beta receptor affinity or numbers. Meta-static progression was, therefore, associated with an increase in the secretion of activated TGF-beta(1), and a loss of the ability to deregulate TGF-beta-responsive genes.

引用

页码：115 / 127

页数：13

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