In situ expression of transforming growth factor ?? is associated with melanoma progression and correlates with Ki67, HLA-DR and ?? 3 integrin expression

Moretti, Silvia; Pinzi, Cinzia; Berti, Emilio; Spallanzani, Adelina; Chiarugi, Alberto; Boddi, Vieri; Reali, Umberto Maria; Giannotti, B.

doi:10.1097/00008390-199708000-00006

Cited by 73 publications

(45 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, whereas TGF-ß1 in situ expression was significantly higher only in high dysplastic polyps, a progressive increase in TGF-ß1 transcript and protein accumulation was observed in successive stages of the colorectal tumor progression. TGF-ß1 has been found to be overexpressed locally in various types of solid tumors, including cancer of the breast (70), colon (71,72), esophagus (73), stomach (74), pancreas (75), liver (76), lung (77), prostate (78), brain (79), and malignant melanoma (80). Overexpression is frequently correlated with advanced tumor stage, metastases and a poorer overall prognosis.…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Bellone

Gramigni²,

Vizio³

et al. 2010

Int J Oncol

View full text Add to dashboard Cite

Abstract. The precise timing of the angiogenic switch in colorectal cancer development is still unclear. The simultaneous expression of Endoglin (CD105), transforming growth factor (TGF)-ß1 and TGF-ß receptor (R) II were quantified in surgical specimens comprising normal human colon, pre-malignant dysplastic tissue, in situ, and invasive colon cancer specimens, at mRNA and protein levels, respectively by real-time PCR and immunohistochemistry. Serum concentrations of soluble Endoglin and TGF-ß1 were evaluated. mRNA and CD105 + -microvessel density (MVD) increased significantly in dysplastic colon and carcinoma versus normal tissues; values correlated respectively with dysplasia degree and Dukes' stages. TGF-ß1 expression was significantly upregulated in most severe dysplastic adenoma specimens, while TGF-ß1 transcript and protein signals were intense in carcinoma, positively-correlated with tumor progression. TGF-ß1 RII was overexpressed in adenoma and carcinoma versus normal samples, but unrelated with dysplasia or Dukes' stage. Soluble Endoglin serum levels were equivalent in adenoma and normal tissues; in carcinoma the highest levels were in invasive tumor. Circulating TGF-ß1 levels were increased in severe dysplasia and progressed with tumor progression. Correlations between adenoma dysplasia degree and TGF-ß RII and CD105 + -MVD, and between tumor Dukes' staging and TGF-ß1 and CD105 + -MVD, were significant. TGF-ß1 and Endoglin and TGF-ß1 serum levels, TGF-ß1 staining and CD105 + -MVD were significantly and inversely associated with disease-free survival. TGF-ß1 levels were an independent and significant prognostic factor of disease-free survival. These findings suggest active angiogenesis occurs in many pre-malignant colon cases and supports more careful evaluation of different chemopreventive agents.

show abstract

Section: Discussionmentioning

confidence: 99%

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Bellone

Gramigni²,

Vizio³

et al. 2010

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Therefore, any insight into the mechanisms of melanoma cell metastasis may contribute to the development of more effective and specific strategies to interfere with melanoma progression. Melanoma cells begin to express the adhesion receptor integrin a V b 3 at the onset of invasive tumor growth in the skin (Moretti et al, 1997). The receptor strongly supports melanoma tumorigenicity in vivo (Felding-Habermann et al, 1992) and melanoma cell survival and proliferation in vitro (Montgomery et al, 1994).…”

Section: Introductionmentioning

confidence: 91%

JWA regulates melanoma metastasis by integrin αVβ3 signaling

Bai

Zhang

et al. 2009

Oncogene

View full text Add to dashboard Cite

JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As 2 O 3 ) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As 2 O 3 on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin a V b 3 signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma.

show abstract

“…While constitutive HLA class II antigen expression was reported to be associated with a favorable prognosis in some tumor types, e. g. CRC and larynx squamous cell carcinoma, [71][72][73][74] it was associated with higher metastatic dissemination, increased tumor stage and reduced patients' survival in other malignancies, such as melanoma and cervical carcinoma. [75][76][77] Conflicting is the information about the clinical relevance of HLA class II antigen expression in osteosarcoma; however, the number of tumors analyzed is too small to draw conclusions. 78,79 In addition, even within defined cancer types, the prognostic value of HLA class II antigens is conflicting depending on the studies.…”

Section: Deregulation Of Hla Class II Apm Components In Malignant Cellsmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

View full text Add to dashboard Cite

The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4 C T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4 C T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.

show abstract

In situ expression of transforming growth factor ?? is associated with melanoma progression and correlates with Ki67, HLA-DR and ?? 3 integrin expression

Cited by 73 publications

References 0 publications

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

JWA regulates melanoma metastasis by integrin αVβ3 signaling

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

Contact Info

Product

Resources

About