Synthesis and secretion of an epidermal growth factor (EGF) by human fibroblast cells in culture

Kurobe, Masayuki; Furukawa, Shoei; Hayashi, Kyozo

doi:10.1016/0006-291x(85)90201-3

Cited by 36 publications

(17 citation statements)

References 12 publications

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“…Foreskin fibroblasts grow in plasma but are stimulated to grow by hydrocortisone, suggesting a different mechanism for their reduced requirement for serum growth factors. Production of EGF has been reported for foreskin fibroblasts but not for other dermal fibroblasts (40).…”

Section: Methodsmentioning

confidence: 94%

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.

Russell

Trupin

Rodriguez-Eaton

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

109

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Section: Methodsmentioning

confidence: 94%

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.

Russell

Trupin

Rodriguez-Eaton

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

109

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“…For example, CXCL12 produced by tumor-associated fibroblasts 18 outside of the tumor could result in gradients of CXCL12 directing tumor cell invasion out from the primary tumor in an EGFR-dependent fashion. There are multiple sources of EGF in the local microenvironment, such as macrophages, 15 fibroblasts, 17 or activated platelets, 16,55 and we find that EGF gradients will also direct in vivo invasion. Thus, our results support treatment of HNSCC with EGFR inhibitors to inhibit local invasion independent of effects on tumor growth rate.…”

Section: In Vivo Invasion Of Hnscc 2863mentioning

confidence: 64%

“…Stromal cells are known to release chemotactic signals that drive invasion of tumor cells further into host stoma. For example, tumor-associated macrophages, fibroblasts, or platelets can produce EGFR ligands such as EGF, [15][16][17] whereas tumor-associated fibroblasts can produce CXCL12. 18 Macrophages express the CXCL12 receptor CXCR4, whereas tumor cells can express both EGFR and CXCR4.…”

mentioning

confidence: 99%

In Vivo Invasion of Head and Neck Squamous Cell Carcinoma Cells Does Not Require Macrophages

Смирнова

Adomako

Locker

et al. 2011

The American Journal of Pathology

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Invasion of tumor cells into the local stroma is an important component in cancer progression.Here we report studies of the in vivo invasion of head and neck squamous cell carcinoma (HNSCC) cells in response to applied gradients of a growth factor [epidermal growth factor (EGF)] and a chemokine (CXCL12), using orthotopic floor-of-mouth models. Analysis of the invading cells indicated that >75% of them were tumor cells, about 15% macrophages, and <10% were unidentified. Surprisingly, although macrophages invaded together with tumor cells, macrophage contributions were not required for HNSCC invasion. CXCL12-induced in vivo invasion of HNSCC cells was also observed and found to occur via a unidirectional transactivation of epidermal growth factor receptor (EGFR) through CXCR4. Inhibition of tumor necrosis factor-␣-converting enzyme using TNF-␣ protease inhibitor-2 selectively inhibited CXCL12-induced invasion but not EGF-induced invasion, consistent with CXCL12 activation of EGFR via release of EGFR ligands. Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common types of cancer in the world, with over 500,000 new cases per year and 250,000 deaths worldwide as estimated by the World Health Organization. This includes 48,000 new cases and 11,260 deaths in 2009 from HNSCC in the United States. 1 HNSCC originates from mucosal tissues of the upper aerodigestive tract and spans the oral cavity to the larynx. Despite some improvements in treatment methods, the 5-year survival rate remains just above 50%. 1 Current treatments for HNSCC include single and multimodality therapies using surgical and nonsurgical approaches (chemotherapy and/or radiotherapy). 2 A key constraint that limits the ability of surgical treatment to cure HNSCC is the location-adequate margins to guarantee removal of all tumor cells are difficult to achieve in many cases without severely compromising quality of life or survival. Thus, the degree to which tumor cells have locally spread from the primary tumor can impact the likelihood of recurrence. Indeed, morphological examination of HNSCC has revealed that the pattern of tumor invasion, presence of perineural invasion, and presence of inflammatory cells correlate with clinical outcome. [3][4][5][6] Understanding the mechanisms underlying HNSCC invasion could provide an opportunity to reduce local invasion and improve patient outcome. The epidermal growth factor receptor (EGFR) is often overexpressed in HNSCC 7,8 and correlated with poor prognosis. 9 In addition to driving proliferation, the EGFR has the potential to drive invasion. EGFR ligands are chemoattractants, stimulating directly cell motility and HNSCC invasion in vitro. 10 -12 Studies of EGFR function in HNSCC in vivo have focused on tumor growth, 13,14 and direct evaluation of EGFR-mediated invasion in vivo has been poorly explored.

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“…For example, primary cultures of human mammary stromal fibroblasts have been shown to synthesize and secrete an EGF-like activity in response to estrogen which can be detected following immunoprecipitation with anti-bodies against human EGF (23). In addition, human foreskin fibroblasts recently have been demonstrated to synthesize and secrete low but detectable levels of immunoreactive human EGF, which can be measured with a highly sensitive enzyme immunoassay capable of detecting as little as 0.1pg of human EGF/assay (24). Therefore, until biosynthetic labeling studies are conducted with primary human mammary epithelial cells and with the human breast cancer cell lines, we cannot entirely rule out the possibility that low levels of EGF are also being elaborated by these cells.…”

Section: Discussionmentioning

confidence: 99%

Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells

Perroteau

Salomon

Bortoli

et al. 1986

Breast Cancer Res Tr

102

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Alpha transforming growth factors (alpha TGFs) were immunologically detected in the concentrated conditioned medium (CM) prepared from four human breast cancer cell lines and from primary cultures of human mammary epithelial cells, and in the tissue extracts prepared from normal, benign, and malignant breast biopsies. Immunoreactive alpha TGFs were quantitated by a competitive radioimmunoassay (RIA) using affinity-purified polyclonal sheep anti-rat alpha TGF antibodies which react with human alpha TGF but not with human epidermal growth factor (EGF). The relative level of RIA-detectable alpha TGFs in the CM from the breast cancer cell lines MCF-7, ZR-75-1, T47-D, and MDA-MB-231, and from the CM of primary cultures of human mammary epithelial cells, ranged from 0.02 to 0.85 ng/ml. MCF-7 or ZR-75-1 cells grown in the presence of 17 beta-estradiol (10(-8) M) for 48 h were found to release two- to three-fold more alpha TGFs into their CM than the same cells grown in the absence of estrogen. In detergent extracts prepared from normal breast tissue, a benign fibrocystic lesion, fibroadenomas and primary breast carcinomas, the relative alpha TGF concentrations were found to range from 1.5 to 6 ng/mg cell protein. No significant correlations were found between the alpha TGF levels and the pathological state of the tissues, the estrogen receptor status of the tumors, or the relative amounts of the ras gene protein p21ras in the tissues as determined by Western immunoblot analysis. The question of biological relevancy of alpha TGF for human mammary tumors will require further studies on synthesis and turnover of alpha TGF, the relationship between immunoreactivity and biological activity of alpha TGF, and differences in biological responsiveness of mammary tumor cells.

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Synthesis and secretion of an epidermal growth factor (EGF) by human fibroblast cells in culture

Cited by 36 publications

References 12 publications

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.

In Vivo Invasion of Head and Neck Squamous Cell Carcinoma Cells Does Not Require Macrophages

Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells

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