In this report, we have examined the role of nm23 in two HT29 colon carcinoma sublines at different stages in tumor progression with different responses to TGF beta 1: the HD3 subline, which shows TGF beta 1-induced growth arrest and differentiation; and the more invasive and tumorigenic U9 subline, which induces tumors 7-fold as large as those induced by HD3 cells with one-half the latency.
In an earlier study we decreased nm23 mRNA levels 2- to 8-fold by antisense phosphorothiolated oligonucleotides in two HT29 colon carcinoma sublines at different stages in tumor progression with different responses to TGF beta 1: the HD3 subline, which shows TGF beta 1-induced growth arrest and differentiation; and the more tumorigenic U9 subline, whose growth and invasion are stimulated by TGF beta 1.
Transforming growth factor-beta 1 may play an important role in the early stages of human bladder cancer development, and TGF-beta 1 expression could provide a new relevant tumor marker for determining tumor progression in patients with bladder cancer.
This screen also identified several growth factors such as insulin-like growth factor-II, platelet-derived growth factor-A, and transforming growth factor-beta1, which have previously been implicated in enhancing tumor progression.
After PDX transfection the cells were less efficient in processing the tumor progression-associated furin substrates transforming growth factor beta1 and pro-membrane type 1-MMP.
In the present study we examined the coordinated expression of transforming growth factor-beta-1 (TGF-beta1), its signaling receptors, and its downstream mediator-connective tissue growth factor (CTGF)--and their impact on tumor progression and fibrogenesis in esophageal carcinomas.
A decreased expression of TGFbeta receptors (TbetaR) has been associated with loss of TGFbeta sensitivity and enhanced tumor progression in many types of cancer.
The constant low concentration of TGF-beta1 in the tumour mass may be related to the low content of antiproliferative HNE observed in colon cancer: the latter phenomenon, which reduces TGF-beta1 production in the tumour area, may represent a favourable condition for neoplastic progression.
Here, we show that the serum glycoprotein alpha2-HS-glycoprotein (AHSG) blocks TGF-beta1 binding to cell surface receptors, suppresses TGF-beta signal transduction, and inhibits TGF-beta-induced epithelial-mesenchymal transition, suggesting that AHSG may play a role in tumor progression.
We found that in pancreatic cancer cells Smad proteins and Sp1 cooperatively regulate expression of a distinct set of TGFbeta target genes potentially involved in tumor progression, including MMP-11, cyclin D1 and Smad7.
Animal experiments suggest that TGF-beta1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression.
Since decreased expression of ICAM-1 has been known to contribute to cancer cell escape from immunologic recognition and cytotoxicity by effector cells, the present results indicate that unknown function of TGF-beta1 in the tumor progression and metastasis of pancreatic cancer.
This suggests that genotypes provisionally associated with low expression of pro-inflammatory and immunomodulatory TNF-alpha, IFN-gamma and IL-6 and anti-inflammatory IL-10 and TGF-beta1 could be involved in the mechanisms of cancer progression and escape from immunosurveillance.
Transforming growth factor beta 1 (TGF-beta1) is a potent tumor suppressor but, paradoxically, TGF-beta1 enhances tumor growth and metastasis in the late stages of cancer progression.
In the present study, SD-208, a 2,4-disubstituted pteridine, ATP-competitive inhibitor of the TGFbeta receptor I kinase (TGFbetaRI), was used to inhibit cellular activities and tumor progression of PANC-1, a human pancreatic tumor line.