Transforming growth factor-? signaling in cancer

Rich, Jeremy; Borton, Anita J.; Wang, Xiao Fan

doi:10.1002/1097-0029(20010215)52:4<363::aid-jemt1021>3.0.co;2-f

Cited by 53 publications

(35 citation statements)

References 179 publications

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“…The lack of a statistical significance is likely to be the result of having a relatively small number of patients in each group and a large variation in the TGFb3 levels. With respect to TGFb1, although published data show inconsistency, it is generally accepted that TGFb1 acts as a tumour suppressor, particularly at an early stage of the disease (Rich et al, 2001). A lower TGFb1 level was observed in patients with colorectal cancer compared with controls, which may have been resulted from the elevated CD105/ TGFb1 complex levels in the same patients.…”

Section: Discussionmentioning

confidence: 96%

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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CD105 and its ligand transforming growth factor b (TGFb) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40 -9.00) and 3.10 (range 0.90 -8.00), respectively. Kaplan -Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFb1 and TGFb3 together with the receptor -ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFb1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFb1 level was noted in patients with carcinoma over the controls. Furthermore, TGFb3 and CD105/ TGFb3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFb1 was expressed in cancer cells but TGFb3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFb1, TGFb3 and CD105/TGFb complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

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Section: Discussionmentioning

confidence: 96%

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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“…In both experiments, reduction in the average tumor number per mouse in Eng þ /À versus Eng þ / þ mice is statistically significant when the tumor numbers reach the plateau. Thus, for example, at weeks 22 and 23 in experiment 1 (P-values o0.05 and o0.01, respectively, using a Student t-test) and at weeks 17 and 18 in experiment 2 (Po0.05 and P ¼ 0.01, respectively) Skin carcinogenesis in Endoglin heterozygous mice M Quintanilla et al in carcinogenesis (Akhurst and Balmain, 1999;Massague´et al, 2000;Derynck et al, 2001;Rich et al, 2001). TGF-b 1 acts as a suppressor of tumor formation, early in carcinogenesis -by virtue of its well-established antimitogenic function in epithelial cells (Roberts and Sporn, 1990;Alexandrov and Moses, 1995).…”

Section: Discussionmentioning

confidence: 99%

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

et al. 2003

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Endoglin is an integral membrane glycoprotein primarily expressed in the vascular endothelium, but also found on macrophages and stromal cells. It binds several members of the transforming growth factor (TGF)-b family of growth factors and modulates TGF-b 1 -dependent cellular responses. However, it lacks cytoplasmic signaling motifs and is considered as an auxiliary receptor for TGF-b. We show here that endoglin is expressed in mouse and human epidermis and in skin appendages, such as hair follicles and sweat glands, as determined by immunohistochemistry. In normal interfollicular epidermis, endoglin was restricted to basal keratinocytes and absent in differentiating cells of suprabasal layers. Follicular expression of endoglin was high in hair bulb keratinocytes, but decreased in parts distal from the bulb. To address the role of endoglin in skin carcinogenesis in vivo, Endoglin heterozygous mice were subjected to long-term chemical carcinogenesis treatment. Reduction in endoglin had a dual effect during multistage carcinogenesis, by inhibiting the early appearance of benign papillomas, but increasing malignant progression to highly undifferentiated carcinomas. Our results are strikingly similar to those previously reported for transgenic mice overexpressing TGF-b 1 in the epidermis. These data suggest that endoglin might attenuate TGF-b 1 signaling in normal epidermis and interfere with progression of skin carcinogenesis.

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“…During the early stages of cancer, TGF-β1 functions as a tsumor suppressor by inhibiting cellular proliferation and thus promoting cellular differentiation or apoptosis (Blobe et al, 2000;Rich et al, 2001;Derynck et al, 2001;Siegel et al, 2003). In contrast, it acts as a tumor promoter to accelerate tumor progression and metastasis during the progressive stage of cancer.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Protein Expression in Non-Small Cell Lung Cancers is Correlated with Prognosis

Huang¹,

Liu²,

Qi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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To investigate the expression intensity and prognostic significance of TGF-β1 protein in non-small cell lung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normal lung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-β1 protein expression in systematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-β1 PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated with TNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history, tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated that patients with high TGF-β1 protein expression and lymph node metastases demonstrated a poor prognosis (both p=0.000, ). Multivariate analysis showed that TGF-β1 protein expression (RR = 2.565, p=0.002) and lymph node metastases (RR=1.874, p= 0.030) were also independent prognostic factors. Thus, TGF-β1 protein expression may be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC.

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Transforming growth factor-? signaling in cancer

Cited by 53 publications

References 179 publications

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

TGF-β1 Protein Expression in Non-Small Cell Lung Cancers is Correlated with Prognosis

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