Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts.

Grey, Ann Marie; Schor, Ana M.; Rushton, Graham; Ellis, Ian R.; Schor, Seth L.

doi:10.1073/pnas.86.7.2438

Cited by 135 publications

(64 citation statements)

References 27 publications

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“…19 For example, they may develop smooth muscle differentiation (myofibroblasts) 27 with increased motility into collagen gel 28 and soluble migration stimulation factor (MSF) secretion. 29 A recent study even showed that normal-appearing stromal cells within breast cancer tissues underwent loss of heterozygosity (LOH) in several loci, whereas no LOH was observed in the stromal cells from reduction mammoplasty (without cancer). 30 These tumor-associated fibroblasts have been designated by some investigators as "activated," 31 "abnormal" 29 or "reactive" 32 in malignant breast tumors.…”

Section: Discussionmentioning

confidence: 99%

Stromelysin‐3 expression by mammary tumor‐associated fibroblasts under in vitro breast cancer cell induction

Wang

Têtu

2002

Intl Journal of Cancer

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To understand better the influence of the host stromal phenotype on stromal expression of stromelysin-3 (ST3) in breast cancer, we have investigated ST3 expression by host stromal cells isolated from 9 different primary breast carcinomas. These tumor-associated fibroblasts were cocultivated with 3 epithelial cancer cell lines of mammary origin (MDA-MB-231, SK-BR-3 and MCF-7), as well as with normal human mammary epithelial cells (NME and 184A1) and keratinocytes, using both direct and indirect coculture systems. ST3 expression was demonstrated by both in situ hybridization and immunocytochemistry. The results showed that ST3 expression by stromal cells was cancer-specific. Indeed, ST3 expression by tumor-associated stromal cells was induced by 3 malignant cancer cell lines (MDA-MB-231, SK-BR-3 and MCF-7), whereas no ST3 was expressed under normal mammary epithelial cell stimulation. ST3 expression was weak or absent in unstimulated tumor-associated fibroblasts. However, after direct coculture with cancer cells, expression of ST3 transcripts reappeared in 8 of the 9 cases and was observed only in fibroblasts located in close contact with tumor cells. Under similar coculture conditions and using the same cancer cell line stimulation, ST3 expression was, however, quite variable among these 9 cases, reflecting the difference of protease expression observed on the sections of the original tumors. Tumor induction of ST3 expression was much more important by direct cell-cell contact than by indirect stimulation and was not influenced by the addition of basic fibroblast growth factor (bFGF) and antibFGF to the culture medium. Our results suggest that the host stromal cell phenotype may significantly influence host stromal cell protease expression under cancer cell stimulation.

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Section: Discussionmentioning

confidence: 99%

Stromelysin‐3 expression by mammary tumor‐associated fibroblasts under in vitro breast cancer cell induction

Wang

Têtu

2002

Intl Journal of Cancer

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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: 84%

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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“…Several investigators reported that stromal alterations precede the malignant progression of tumor cells, 4,5 and that local and mutual interactions between cancer cells and stromal cells, such as fibroblasts, macrophages, lymphocytes, neutrophils, and endothelial cells, are important for regulating the extracellular matrix degradation, angiogenesis, and migration and invasion of tumor cells. 6 Concerning cancer-stromal interaction in oral SCC, Matsumoto et al 7 and Sugiura et al 8 reported that gingival fibroblasts markedly enhanced the invasion of oral SCC cells in vitro.…”

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confidence: 99%

Role of HGF/c-met system in invasion and metastasis of oral squamous cell carcinoma cellsin vitro and its clinical significance

et al. 2001

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We examined the role of the hepatocyte growth factor (HGF)/c-met system on invasion and metastasis of oral squamous cell carcinoma (SCC) cells. In monolayer culture, exogenous HGF marginally affected the growth of oral SCC cells (BHY, HN, IH) and human gingival epithelial cells (GE). In type I collagen matrix, however, HGF significantly enhanced the invasive growth of the cancer cells (p < 0.05). We detected the expression of c-met (HGF receptor) mRNA in all of the cancer cells, but not in human gingival fibroblasts (GF). Oral SCC cells did not secret HGF protein into the medium, but GF secreted a large amount of HGF protein (15 ng/ml). Furthermore, HGF markedly enhanced the migration of cancer cells in a Transwell invasion chamber. Then, we examined the serum levels of HGF in oral SCC patients, or HGF concentrations in oral cancer tissues. Serum levels of HGF in the patients were significantly higher than those in healthy volunteers (p < 0.05). After initial treatment, all of the tumor-free survivors showed a marked decline in the serum HGF levels. Furthermore, HGF concentrations in metastatic cancer tissues were significantly higher than those of nonmetastatic cancer tissues and normal gingiva (p < 0.01). These results suggest that HGF plays an important role in invasion and metastasis of oral SCC cells as a paracrine factor, and an elevated HGF level in the cancer tissue can be a predictive marker for metastasis formation in patients with oral SCC. © 2001 Wiley-Liss, Inc. Key words: oral SCC; HGF; c-met; metastasisOral SCCs are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes, but a low rate of metastases to distant organs. Moreover, oral SCC frequently show local recurrence after initial treatment, probably due to micro-invasion or micro-metastasis of the tumor cells at the primary site. We recently reported that oral SCC cells produced a large amount of matrix-degrading enzymes and that the net activity of MMP2 (active-MMP2/TIMP2) produced by cancer cells contributes to lymph-node metastasis in a nude-mouse orthotopic inoculation model. 1 We also noted that cancer cells in the peripheral blood of patients with oral SCC were frequently detected by RT-PCR for cytokeratin 20 mRNA, and that there was no clear relationship between the hematogenous cancer cells and the metastasis. 2 Furthermore, by microdissection zymography, we demonstrated that active MMP2 in cancer cell nests could be a predictive marker for metastasis formation in patients with oral SCC. 3 The precise molecular mechanisms of invasion and metastasis of oral cancer, however, especially the interaction between cancer cells and host cells, are still unknown.

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Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts.

Cited by 135 publications

References 27 publications

Stromelysin‐3 expression by mammary tumor‐associated fibroblasts under in vitro breast cancer cell induction

Stromelysin‐3 expression by mammary tumor‐associated fibroblasts under in vitro breast cancer cell induction

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

Role of HGF/c-met system in invasion and metastasis of oral squamous cell carcinoma cellsin vitro and its clinical significance

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