Phenotypic alterations in fibroblasts and fibrosarcoma cells that overexpress latent transforming growth factor-beta 1.

Beauchamp, R. Daniel; Sheng, Hongmiao; Bascom, Charles C.; Miller, Diana S.; Lyons, Russette M.; Torre‐Amione, Guillermo; Moses, Harold L.

doi:10.1210/endo.130.5.1374006

Cited by 11 publications

(4 citation statements)

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“…Our results confirm that cancer cells may attain immune escape by changing the effector composition of the host immune cells. We further explore the issues of proposed cancer-host immune interactions based on previous in vivo murine models and in vitro cell line results (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

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Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Sheu

Lin

Lien

et al. 2001

The Journal of Immunology

181

115

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Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN-γ in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-β plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-β Abs. IL-10 and TGF-β are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF-β in cancer-mediated immunosuppression.

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Section: Discussionmentioning

confidence: 99%

“…TGF-␤ and IL-10 are secreted spontaneously by a variety of human malignant tumors, including breast, colon, ovary, cutaneous basal/squamous cancers, metastatic melanoma, fibrosarcoma, and pancreatic carcinoma (27)(28)(29)(30)(31)(32)(33)(34)(35). The mechanisms responsible for the increased expression by tumor cells are not known.…”

Section: Discussionmentioning

confidence: 99%

Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Sheu

Lin

Lien

et al. 2001

The Journal of Immunology

181

115

View full text Add to dashboard Cite

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“…This is likely due to the fact that the cells not only produce high levels of one or more TGF␤ isoforms, but also can activate them. In TGF␤ 1 -transfected fibroblasts and fibrosarcoma cells, it was found that a significant amount of cell-activated TGF␤ 1 was bound to the cell surface even though very little activated TGF␤ 1 could be detected in the conditioned medium (43). The MCF-7 cells we used produced a readily detectable amount of mature, activated TGF␤ 1 in the conditioned medium as shown in Fig.…”

Section: Resultsmentioning

confidence: 92%

Expression of Transforming Growth Factor β (TGFβ) Type III Receptor Restores Autocrine TGFβ1 Activity in Human Breast Cancer MCF-7 Cells

Chen

Wang

Sun

1997

Journal of Biological Chemistry

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While transforming growth factor ␤ (TGF␤) type III receptor (RIII) is known to increase TGF␤ 1 binding to its type II receptor (RII), the significance of this phenomenon is not known. We used human breast cancer MCF-7 cells to study the role of RIII in regulating autocrine TGF␤ 1 activity because they express very little RIII and no detectable autocrine TGF␤ activity. A tetracyclinerepressible RIII expression vector was stably transfected into this cell line. Expression of RIII increased TGF␤ 1 binding to TGF␤ type I receptor (RI) as well as RII. Treatment with tetracycline suppressed RIII expression and abolished TGF␤ 1 binding to RI and RII. Growth of RIII-transfected cells was reduced by 40% when plated at low density on plastic. This reduction was reversed by tetracycline treatment and was partially reversed by treatment with a TGF␤ 1 neutralizing antibody. The activity of a TGF␤-responsive promoter construct when transiently transfected was more than 3-fold higher in the RIII-transfected cells than in the control cells. Treating the cells with tetracycline or the TGF␤ 1 neutralizing antibody also significantly attenuated the increased promoter activity. These results suggest that expression of RIII restored autocrine TGF␤ 1 activity in MCF-7 cells. The RIII-transfected cells were also much less clonogenic in soft agarose than the control cells indicating a reversion of progression. Thus, RIII may be essential for an optimal level of the autocrine TGF␤ activity in some cells, especially in the transformed cells with reduced RII expression.Transforming growth factor ␤ (TGF␤) 1 isoforms are homodimer polypeptides of 25 kDa. They are multifunctional growth factors involved in the regulation of cell proliferation, differentiation, extracellular matrix formation, and immune response (1-3). Many studies have shown that TGF␤ can inhibit the growth of a variety cell types including epithelial, endothelial, lymphoid, and myeloid cells (4). Almost all types of cells express one or more of the three isoforms identified in mammals. Although in most systems, the majority of TGF␤s secreted is in a latent form with no biological activity, a small percentage can be detected as mature, active TGF␤s which may act to regulate cellular functions in an autocrine fashion. For example, neutralization of endogenous TGF␤s with anti-TGF␤ antibodies was shown to stimulate proliferation of breast and colon cancer cells (5-7). Repression of TGF␤ expression by TGF␤1 antisense RNA in colon cancer cells was shown to increase clonogenicity in soft agarose and tumorigenicity in nude mice indicating that autocrine TGF␤ activity is tumorsuppressive (8, 9).TGF␤s elicit their effects by binding mainly to three cell surface proteins termed type I (RI), type II (RII), and type III (RIII) receptors. RI and RII are serine/threonine kinase receptors of 55 and 75 kDa, respectively, that form heteromeric complex, apparently at one to one stoichiometric ratio and necessary for TGF␤ signal transduction (3). It has been shown that RI requires RII for TGF␤...

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“…This is a polysulfonated naphthylurea used in the therapy of trypanosomiasis and onchocerciasis. It noncompetitively inhibits binding of exogenous PDGF (Hosang, 19851, EGF (Coffey et al, 19871, IGF-1 (Pollack and Richard, 19901, and transforming growth factor beta (TGFP; Beauchamp et al, 1992) to their receptors and prevents transformation by v-sis, presumably by inhibiting binding of the endogenously produced sis protein to its receptor (Betsholtz et al, 1986). While suggestions have been made that like other polyanionic compounds it inhibits protein kinase C (Powis, 1991), this…”

Section: Discussionmentioning

confidence: 99%

Peripheral and central vascular smooth muscle cells from rat lung exhibit different cytoskeletal protein profiles but similar growth factor requirements

Davies

Patton²

1994

Journal Cellular Physiology

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In pulmonary vascular remodelling, the lining smooth muscle cells undergo various forms of growth involving cellular hypertrophy and hyperplasia. Differences in the growth pattern between central and peripheral regions suggested that cells from both should be obtained when investigating the cellular basis for the remodelling. Accordingly, we have obtained two smooth muscle cell types in culture: a cell from the central pulmonary artery (CC) and a cell morphologically similar to a pericyte (PC), from the periphery of the lung. Both cell types gave positive immunostaining for alpha-smooth muscle isoactin. In vivo, the alpha-isoactin was immunolocalized in the extracapillary vasculature. Quantitative two-dimensional gel electrophoresis of cell extracts showed that PC express more vimentin and gelsolin than CC. Despite the differences between PC and CC in the expression of cytoskeletal proteins, their response to growth factors was similar. Both cell types increased DNA synthesis when stimulated by exogenous PDGF-AB. This occurred in the absence of exogenous progression factors, but depended on a post-competence, suramin-sensitive mechanism that probably represents an autocrine progression factor. The cells were also stimulated by IGF-1 alone, in the absence of exogenous competence factors. At an IGF-1 concentration of 1 ng/ml, this response appeared specific for the IGF-1 receptor and was sensitive to pretreatment with pertussis toxin, thus implicating a role for a G protein.

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Phenotypic alterations in fibroblasts and fibrosarcoma cells that overexpress latent transforming growth factor-beta 1.

Cited by 11 publications

References 46 publications

Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer

Expression of Transforming Growth Factor β (TGFβ) Type III Receptor Restores Autocrine TGFβ1 Activity in Human Breast Cancer MCF-7 Cells

Peripheral and central vascular smooth muscle cells from rat lung exhibit different cytoskeletal protein profiles but similar growth factor requirements

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