Expression of fibronectin, fibronectin isoforms and integrin receptors in melanocytic lesions

Natali, Pier Giorgio; Nicotra, Maria Rita; Filippo, F. Di; Bigotti, A.

doi:10.1038/bjc.1995.240

Cited by 46 publications

(38 citation statements)

References 34 publications

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“…Interestingly, several genes known to be important and strongly overexpressed in malignant melanoma were shown to be downregulated in MIA-deficient cell clones: t-PA, SPARC (BM40, osteonectin), MT1-MMP, integrin b3 and fibronectin. A large body of evidence suggests a role for t-PA (Saksela et al, 1984;Meissauer et al, 1991;Alizadeh et al, 1995;de Vries et al, 1996), SPARC (Ledda et al, 1997a, b;Massi et al, 1999;Sturm et al, 2002), MT1-MMP (Hofmann et al, 2000a, b;Seftor et al, 2001;Krengel et al, 2002;Sounni et al, 2002;Iida et al, 2004), integrin b3 (Nip et al, 1992;Natali et al, 1995;Van Belle et al, 1999;Felding-Habermann et al, 2002;Sturm et al, 2002) and fibronectin (Wollina et al, 1991;Natali et al, 1995) in migration, invasion and metastatic spread of melanoma cells. Since these proteins are directly or indirectly involved in matrix degradation (t-PA, MT1-MMP), in the transition of melanomas being in radial growth phase to a vertical growth phase (induction of SPARC by integrin b3) and enforced cell proliferation (fibronectin), induction of gene expression by MIA could account for several abilities that melanoma cells harbor during tumor development and progression.…”

Section: Discussionmentioning

confidence: 99%

Functional role of MIA in melanocytes and early development of melanoma

et al. 2004

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The protein MIA (melanoma inhibitory activity) is highly expressed in malignant melanomas but not in melanocytes. Furthermore, expression of MIA correlates with tumor progression in vivo. Here, MIA-dependent changes of gene expression after long-term inhibition of MIA expression in the human melanoma cell line HMB2 were investigated. Primarily, we observed characteristic changes in cell morphology, and also found re-established cell-cell contacts in MIA-deficient cell clones grown in monolayer culture. Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed a downregulation of N-cadherin expression and a reinduction of E-cadherin expression in the MIA-deficient cell clones. Further, both cancer cDNA array and protein arrays verified a marked downregulation of several other melanoma-associated genes (e.g. membrane-type 1 matrix metalloproteinase tissue-type plasminogen activator integrin b3, secreted protein acidic and rich in cysteins and fibronectin) in the MIA-deficient melanoma cells, confirmed by real-time RT-PCR and Western blotting. As all these molecules are associated with migration, the effect of MIA on migration of human primary melanocytes was analysed. In the presence of MIA, we observed enhanced migratory ability of melanocytic cells, induction of melanoma-associated genes as well as inhibition of apoptosis due to anoikis. These results suggest that expression of MIA promotes melanoma progression by inducing further melanoma-associated genes.

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Section: Discussionmentioning

confidence: 99%

Functional role of MIA in melanocytes and early development of melanoma

et al. 2004

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“…Recently the Fn isoform containing EDA has been shown to be associated to vascular and stromal structures in a wide variety of cancer types. Furthermore, Natali and colleagues described an abundant expression of EDA-Fn in primary melanomas and their metastases (14). A high-affinity human mAb directed to EDA-Fn, F8, has been shown to display tumor-targeting selectivity in biodistribution experiments (15).…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

et al. 2012

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The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma. Cancer Res; 72(7); 1814-24. Ó2012 AACR.

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“…[6][7][8][9] In breast cancers, immunohistochemical studies using specific monoclonal antibodies have demonstrated that FN isoforms, including EDA (EDA + FN) and EDB (EDB + FN) can be detected in cancer stroma. [10][11][12] In contrast, it has been considered that the effect of the splicing may be quantitative rather than qualitative, 13) and the functional significance of molecular differences has yet to be clarified in detail.…”

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Expression of Fibronectin Isoforms in Human Breast Tissue: Production of Extra Domain A⁺/Extra Domain B⁺ by Cancer Cells and Extra Domain A⁺ by Stromal Cells

Matsumoto

Yoshida

Kawarada

et al. 1999

Japanese Journal of Cancer Research

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The expression of fibronectin (FN) isoforms including extra domain A (EDA) and extra domain B (EDB) segments, was investigated in 36 invasiveMany recent studies have demonstrated that FN is upregulated in cancer tissues, with reappearance of alternatively spliced isoforms. [6][7][8][9] In breast cancers, immunohistochemical studies using specific monoclonal antibodies have demonstrated that FN isoforms, including EDA (EDA + FN) and EDB (EDB + FN) can be detected in cancer stroma. [10][11][12] In contrast, it has been considered that the effect of the splicing may be quantitative rather than qualitative, 13) and the functional significance of molecular differences has yet to be clarified in detail. However, recent studies have demonstrated that EDA + FN exhibits a high affinity for integrin, 14) and EDB + isoform induces tyrosine phosphorylation of focal adhesion proteins. 15)To establish the possible roles of different FN isoforms in cancer progression, it is important to clarify the cellular sources of these isoforms. Therefore, we examined mRNA expression of EDA and EDB, and well as total FN isoforms, by in situ hybridization (ISH) using cRNA probes specific to the constant region and alternatively spliced sites, in benign and malignant human breast lesions. MATERIALS AND METHODSTissues A total of 49 human breast tumors (36 invasive ductal carcinomas and 13 benign tumors) were investigated. All tissues were surgically resected, and immediately fixed in 4% paraformaldehyde in 0.1 M phosphate buffer (PB), pH 7.4, at 4°C overnight. After having been rinsed in PB, they were dehydrated through a graded ethanol series and xylene, embedded in paraffin, sectioned at 4 µm, and placed on silane-coated glass slides (Dako Japan, Kyoto).Histological classification was made using sections stained with hematoxylin and eosin. To examine the relationship of expression of FN isoforms to morphological

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Expression of fibronectin, fibronectin isoforms and integrin receptors in melanocytic lesions

Cited by 46 publications

References 34 publications

Functional role of MIA in melanocytes and early development of melanoma

Functional role of MIA in melanocytes and early development of melanoma

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

Expression of Fibronectin Isoforms in Human Breast Tissue: Production of Extra Domain A⁺/Extra Domain B⁺ by Cancer Cells and Extra Domain A⁺ by Stromal Cells

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Expression of fibronectin, fibronectin isoforms and integrin receptors in melanocytic lesions

Cited by 46 publications

References 34 publications

Functional role of MIA in melanocytes and early development of melanoma

Functional role of MIA in melanocytes and early development of melanoma

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

Expression of Fibronectin Isoforms in Human Breast Tissue: Production of Extra Domain A+/Extra Domain B+ by Cancer Cells and Extra Domain A+ by Stromal Cells

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Expression of Fibronectin Isoforms in Human Breast Tissue: Production of Extra Domain A⁺/Extra Domain B⁺ by Cancer Cells and Extra Domain A⁺ by Stromal Cells