Antibody Library-based Tumor Endothelial Cells Surface Proteomic Functional Screen Reveals Migration-stimulating Factor as an Anti-angiogenic Target

Hu, Hai; Ran, Yuliang; Zhang, Yushan; Zhou, Zhuan; Harris, Simon J.; Lan, Yu; Sun, Lixin; Pan, Jian; Li, Jun; Lou, Jinning; Yang, Zhihua

doi:10.1074/mcp.m800331-mcp200

Cited by 24 publications

(22 citation statements)

References 39 publications

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“…It was recently reported that the in vivo biodistribution of a labeled anti-MSF Ab was selectively concentrated in tumor vessels in a mouse model of xenograft esophageal carcinoma (107). Interestingly, administration of the anti-MSF Ab to tumor-bearing mice significantly reduced tumor growth, thus indicating that targeting of MSF in tumors may have therapeutic potential (107).…”

Section: Discussionmentioning

confidence: 99%

Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility

Solinas

Schiarea

Liguori

et al. 2010

The Journal of Immunology

338

292

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Tumor-associated macrophages (TAMs) are key orchestrators of the tumor microenvironment directly affecting neoplastic cell growth, neoangiogenesis, and extracellular matrix remodeling. In turn, the tumor milieu strongly influences maturation of TAMs and shapes several of their features. To address the early macrophage (Mϕ) differentiation phase in a malignant context, we mimicked a tumor microenvironment by in vitro coculturing human blood monocytes with conditioned media from different cancer cell lines. Only 2 out of 16 tumor cell lines induced Mϕ differentiation due to secreted M-CSF isoforms, including high molecular mass species. A global gene profiling of tumor-conditioned Mϕ was performed. Comparison with other datasets (polarized M1-Mϕ, M2-Mϕ, and TAMs isolated from human tumors) highlighted the upregulation of several genes also shared by TAM and M2-polarized Mϕ. The most expressed genes were selenoprotein 1, osteoactivin, osteopontin, and, interestingly, migration-stimulating factor (MSF), a poorly studied oncofoetal isoform of fibronectin. MSF (present in fetal/cancer epithelial and stromal cells but not in healthy tissues) was never identified in Mϕ. MSF production was confirmed by immunohistochemistry in human TAMs. MSF was induced by M-CSF, IL-4, and TGFβ but not by proinflammatory stimuli. RNA and protein analysis clearly demonstrated that it is specifically associated with the M2 polarization of Mϕ. Tumor-conditioned Mϕ-derived MSFs strongly stimulated tumor cell migration, thus contributing to the motile phenotype of neoplastic cells. In conclusion, MSF is a new molecule associated with the M2 polarization of Mϕ and expressed by TAMs. Its biological function may contribute to Mϕ-mediated promotion of cancer cell invasion and metastasis.

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Section: Discussionmentioning

confidence: 99%

Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility

Solinas

Schiarea

Liguori

et al. 2010

The Journal of Immunology

338

292

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“…The latter finding raises the intriguing possibility of selectively inducing the destruction of tumour-induced angiogenic vessels while sparing mature host vessels. Independent evidence supporting a role for MSF in cancer pathogenesis has recently come from the study by Hu et al 21 Using an unbiased proteomic screen, these authors identified MSF as a critical angiogenic factor driving oesophageal cancer progression. Yoshino et al 43 have additionally reported that exposure of a bronchioloalveolar carcinoma cell line to the tobacco carcinogen benzo[a]pyrene resulted in the induction of MSF expression.…”

Section: Msf As a Novel Target For Clinical Interventionmentioning

confidence: 99%

“…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. 20 MSF is expressed by tumour and tumourassociated stromal cells in the majority of tumours examined to date, including common carcinomas, melanomas, and gliomas 20,21 (unpublished observations).…”

Section: Msf: Molecular Characterisation and Diverse Functionalitymentioning

confidence: 99%

“…These cells show a bell-shaped dose response with half-maximal activity manifesting at 0.1-1.0 pg/ml, that is, femtomolar concentrations. MSF also stimulates the migration of non-epithelial tumour cells and displays other bioactivities relevant to tumour progression, such as the upregulation of hyaluronan (HA) synthesis, proteolysis, and induction of angiogenesis 20,21,[27][28][29] (unpublished observations). The angiogenic activity of MSF has been demonstrated in both in vitro and in vivo models.…”

Section: Msf: Molecular Characterisation and Diverse Functionalitymentioning

confidence: 99%

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

Schor

2009

Eye

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“…MSF is an oncofetal regulatory protein constitutively expressed by a variety of cell types during fetal development, not expressed by the majority of cells in the healthy adult, but persistently re-expressed by both carcinoma and associated stromal cells in patients with breast and other human cancers [6][7][8][9][10][11][12]. MSF is a 70 kDa genetically truncated isoform of fibronectin [7].…”

Section: Introductionmentioning

confidence: 99%

Migration Stimulating Factor (MSF): A Novel Biomarker of Breast Cancer Progression

Perrier¹,

Woolston²,

Purdie³

2012

Translational

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Migration Stimulating Factor (MSF) is a novel oncofetal biomarker previously identified in a number of human tumours. The aim of this study was to evaluate the possible association between MSF expression and disease progression in breast cancer. Archival breast tissues examined included malignant tumours (T; n=23), benign tumours or pathologies (B; n=8) and histologically normal breast from either reduction mammoplasties (NB; n=19) or from tumour patients (NB-T; n=18). Sections were stained with MSF-specific antibodies and assessed by consensus of 3-4 independent observers in terms of various MSF indices, which represented overall, epithelial and stromal MSF expression. MSF was heterogeneously expressed by epithelial and stromal cells, with significant inter-group quantitative differences in the sequence NB

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Antibody Library-based Tumor Endothelial Cells Surface Proteomic Functional Screen Reveals Migration-stimulating Factor as an Anti-angiogenic Target

Cited by 24 publications

References 39 publications

Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility

Tumor-Conditioned Macrophages Secrete Migration-Stimulating Factor: A New Marker for M2-Polarization, Influencing Tumor Cell Motility

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

Migration Stimulating Factor (MSF): A Novel Biomarker of Breast Cancer Progression

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