Intense staining for TGF beta 1 correlated significantly (P < 0.0013; odds ratio, 18) with disease progression to metastasis and was independent of nodal status and the degree of differentiation of the primary tumor.
These findings suggest that high growth and invasive activity may play an important role in disseminated metastasis and that EGF and TGF-beta 1, which affect the growth and invasive activity of OCUM-2D cells, might be factors associated with metastasis in scirrhous gastric carcinoma.
nm23 has properties of a metastasis suppressor gene and also has been implicated in the control of response to transforming growth factor beta 1 (TGF beta 1) by studies in melanoma cells.
We analyzed sequences that were differentially stimulated by transforming growth factor-beta1 in primary tumor-versus metastasis-derived cell lines, based on our previous studies indicating that acquisition of differential responses to this growth factor could result in phenotypic traits that facilitate tumor metastasis from specific cell clones within the primary tumor.
Analysis of the metastatic lesions showed that they expressed TGF-beta1 and MMP-2 but barely detectable levels of IL-10 or TIMP-1, suggesting that IL-10 and TIMP-1 might normally block tumor growth, angiogenesis, and metastasis.
Because the serum levels of transforming growth factor-beta1 (TGF-beta1) correlate with outcome in patients with HCC and because TGFbeta1 mRNA expression is increased in HCC tissues, it raises the possibility that TGF-beta1 may be of importance in the development, growth, and metastases of HCC.
We developed a mouse model for colon cancer that identifies an early role for TGF-beta1 in tumor suppression and implicates TGF-beta2 or TGF-beta3 in the prevention of metastasis.
It has been postulated that TGFbeta acts as a tumor suppressor at the early stages of carcinogenesis, but overexpression of TGFbeta at late stages of carcinogenesis may be a critical factor for tumor invasion and metastasis.
Transgene(s) and TGF-beta 1 expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGF-beta signaling, correlated with expression of the DN II R. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene.
We have also demonstrated previously that transforming growth factor-beta1 (TGF-beta1) stimulates urokinase-type plasminogen activator (uPA)-dependent invasion and metastasis of HRA cells.
For patients undergoing radical prostatectomy, preoperative plasma levels of TGF-beta(1) and IL-6sR are associated with metastases to regional lymph nodes, presumed occult metastases at the time of primary treatment, and disease progression.
This TGF-beta1-induced IL-8 expression could be an amplification cascade responsible for overexpression of IL-8 in human melanoma and one of potential mechanisms by which TGF-beta1 promotes angiogenesis, growth, and metastasis of human melanoma.
Moreover, transforming growth factor-beta1 caused a further increase in CTGF expression in these cells.In vivo, the twice weekly i.p. administration of FG-3019 decreased tumor growth and metastasis and attenuated tumor angiogenesis and cancer cell proliferation.
RNAi-mediated knockdown of ILEI in EpRas cells before and after EMT (EpRasXT) prevented and reverted TGFbeta-dependent EMT, also abrogating metastasis formation.
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.
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.
Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine, it promotes tumor growth and metastasis in later stages of phase of cancer development.
Down-regulation or loss of the transforming growth factor-beta1 (TGFbeta1) cytostatic program and activation of TGFbeta-mediated transcriptional networks is associated with uncontrolled growth and metastasis in other neural tumors, glioblastomas.
Transforming growth factor beta1 (TGF-beta1) suppresses tumor development at early stages of cancer, but enhances tumor invasion and formation of metastasis.
Together, these findings suggest that TAK1 contributes to TGF-beta1-mediated tumor angiogenesis and metastasis via a mechanism involving the TAK1-NF-kappaB-MMP-9 pathway.