Fetal and cancer patient fibroblasts secrete a soluble migration stimulating factor not produced by normal adult cells

Schor, Seth L.; Schor, Ana M.; Rushton, Graham; McCormick, Lauren

doi:10.1016/0309-1651(87)90045-2

Cited by 40 publications

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“…It is able to stimulate fibroblast migration in a native collagen-I matrix. 12,13 We provide the first evidence that MSF displays constitutive Fn-proteinase activity. We show that several human breast adenocarcinoma cell lines constitutively express MSF and have an endogenous Fn-proteinase activity.…”

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confidence: 79%

Migration‐stimulating factor displays HEXXH‐dependent catalytic activity important for promoting tumor cell migration

Houard

Germain

Gervais

et al. 2005

Intl Journal of Cancer

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Like most extracellular matrix (ECM) components, fibronectin (Fn) is proteolyzed generating specific activities. Fibronectin proteinase (Fn-proteinase) represents such a cryptic activity located in the gelatin-binding domain (GBD) of Fn and displays a zinc metalloproteinase activity. The migration-stimulating factor (MSF) is a truncated Fn isoform generated by alternative mRNA splicing and corresponds to the N-terminal part of Fn that comprises the GBD. We show that several human mammary epithelial cells express MSF and constitutively produce Fn-proteinase activity. Furthermore, recombinant MSF produced by HEK-293 and MCF-7 cells possesses a constitutive Fn-proteinase activity. Mutating the putative zinc-binding motif, HEXXH, of the protein abolishes its activity thereby demonstrating its specificity. Using PCR, we showed that MSF is barely expressed in normal breast tissues, whereas its expression is significantly increased in tumors. Furthermore, an association between MSF expression and invasive capacity is observed in various breast adenocarcinoma cell lines. Indeed, when stably transfected in non-invasive MCF-7 cells, MSF promotes cell migration in a mechanism mostly dependent on its Fn-proteinase activity. In summary, our study shows that: (i) MSF displays constitutive Fn-proteinase activity; (ii) MSF expression is induced in human breast cancer; and (iii) MSF confers pro-migratory activity that depends mostly on its Fn-proteinase activity. These results suggest that MSF may be involved in tumor progression. ' 2005 Wiley-Liss, Inc.Key words: fibronectin; alternative splicing; Fn-proteinase; migration-stimulating factor; cancer Fibronectin (Fn) is an adhesive glycoprotein, secreted as a dimer, present in body fluids and within extracellular matrices. Each monomer ( 250 kDa) is organized into proteolysis-resistant functional domains. These domains can bind fibrin, collagens, integrins and proteoglycans, accounting for the wide range of Fn functions (Fig. 1a). 1 In addition to these well-characterized properties of ''fulllength'' Fn, proteolytically generated Fn fragments show additional biological activities. For instance, the gelatin-binding domain (GBD) influences cell proliferation and migration, 2 and induces cartilage catabolism. 3 In addition, the GBD isolated after Fn proteolysis or produced in recombinant cells, referred to fibronectin proteinase (Fn-proteinase), 4 displays a zinc-dependent collagenase/gelatinase activity. [5][6][7] Fn-proteinase activity is inhibited by a specific phosphinic pseudo peptide. 5 This activity is involved in the degradation of cartilage induced by the GBD. 8 In addition, we showed recently that Fn-proteinase is activated by plasmin and therefore may play a role in tissue remodeling. 4 Zhao et al. 9 recently cloned and characterized a C-terminus truncated Fn isoform generated by alternative splicing in zebrafish. This isoform, called Fn2, is a 120-kDa monomeric protein with distinct properties compared to ''full-length '' Fn. 9 This raised the possibility that Fn fragm...

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confidence: 79%

Migration‐stimulating factor displays HEXXH‐dependent catalytic activity important for promoting tumor cell migration

Houard

Germain

Gervais

et al. 2005

Intl Journal of Cancer

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“…The observed cytotoxic effect of 3 mg/ml Urtica dioica extract on foreskin fibroblasts might be due to the fact that foreskin fibroblasts are in some characters similar to foetal fibroblasts (Chen et al, 1989). In fact, previous studies indicated that tumor-derived fibroblasts, skin fibroblasts of breast cancer patients and foetal fiboblasts secrete a migration stimulating factor (MSF) which is not secreted by normal fibroblasts (Schor et al, 1988a;1988b). Schor et al (1987) showed that cancer development susceptibility in adults increased in the presence of foetal-like fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

Fattahi

Ardekani²,

Zabihi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r 2 =0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC 50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

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“…16,17 Unexpectedly, MSF-expressing fibroblasts were obtained from both tumour-associated 18 and distant uninvolved sites in cancer patients, thereby indicating the systemic nature of this abnormality. 19 Subsequent ex vivo studies have indicated that both MSF message and protein are expressed by fibroblasts, keratinocytes, and vascular endothelial cells in foetal skin, but not by the majority of these cells in the healthy adult skin.…”

Section: Msf: Molecular Characterisation and Diverse Functionalitymentioning

confidence: 99%

Angiogenesis and tumour progression: migration-stimulating factor as a novel target for clinical intervention

Schor

2009

Eye

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Fetal and cancer patient fibroblasts secrete a soluble migration stimulating factor not produced by normal adult cells

Cited by 40 publications

References 0 publications

Migration‐stimulating factor displays HEXXH‐dependent catalytic activity important for promoting tumor cell migration

Migration‐stimulating factor displays HEXXH‐dependent catalytic activity important for promoting tumor cell migration

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

Angiogenesis and tumour progression: migration-stimulating factor as a novel target for clinical intervention

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