Thrombospondins 1 and 2 function as inhibitors of angiogenesis

Armstrong, Lucas C.; Börnstein, Paul

doi:10.1016/s0945-053x(03)00005-2

Cited by 271 publications

(209 citation statements)

References 59 publications

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“…Because THSD4 is implicated in tumor angiogenesis, it is tempting to speculate that THSD4 affects chemosensitivity through the modulation of tumor angiogenesis. 19 Low mucin 1 (MUC1) expression has been associated significantly with pCR. An inverse correlation between MUC1 expression and chemosensitivity also was reported in colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers

Naoi

Kishi

Tanei

et al. 2011

Cancer

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BACKGROUND. Sequential administration of paclitaxel plus combined fluorouracil, epirubicin, and cyclophosphamide (P-FEC) is 1 of the most common neoadjuvant chemotherapies for patients with primary breast cancer and produces pathologic complete response (pCR) rates of 20% to 30%. However, a predictor of pCR to this chemotherapy has yet to be developed. The authors developed such a predictor by using a proprietary DNA microarray for gene expression analysis of breast tumor tissues. METHODS. Tumor samples were obtained from 84 patients with breast cancer by core-needle biopsy before the patients received P-FEC, and the gene expression profile was analyzed in those samples to construct a classifier for predicting pCR to P-FEC. In addition, the authors analyzed the gene expression profile of tumor tissues that were obtained at surgery from 105 patients with lymph node-negative and estrogen receptor-positive breast cancer who received adjuvant hormone therapy alone to determine the prognostic significance of the classifier. RESULTS. The 70-gene classifier for predicting pCR to P-FEC was constructed by using the training set (n ¼ 50) and subsequently was validated successfully in the validation set (n ¼ 34), revealing high sensitivity (88%; 95% confidence interval [CI], 47%-100%) and high negative predictive value (93%; 95% CI, 68%-100%). Specificity and positive predictive value were 54% (95% CI, 33%-73%) and 37% (95% CI, 16%-62%), respectively. Among the various parameters (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 status, etc), the 70-gene classifier had the strongest association with pCR (P ¼ .015). In an additional study, genetically assumed complete responders were associated significantly (P ¼ .047) with a poor prognosis. CONCLUSIONS. The 70-gene classifier that was constructed for predicting pCR to P-FEC for breast tumors was successful, with high sensitivity and high negative predictive value. The classifier also appeared to be useful for predicting the prognosis of patients with lymph node-negative and estrogen receptor-positive breast cancer who receive adjuvant hormone therapy alone. Cancer 2011;117:3682-

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Section: Discussionmentioning

confidence: 99%

Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers

Naoi

Kishi

Tanei

et al. 2011

Cancer

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“…Retrovirus-mediated expression of TIMP-3 in tumor cells inhib- 145 MMP-2 Various IFN-a 147 EC proliferation/migration Angiostatin 148,149 Various Endostatin 117,150 MT1-MMP, MMP-2 Various Arresten 151 EC proliferation, migration Canstatin 152 EC viability, migration Tumstatin 153,154 EC viability, migration, protein synthesis Platelet factor 4 155 VEGF and bFGF signaling TIMP-1 156 Broad-range Various effects, including MMP inhibition TIMP-2 157 Broad-range Various effects, including MMP inhibition TIMP-3 138 Broad-range Various effects, including MMP inhibition TIMP-4 136 Broad-range Various effects, including MMP inhibition Exogenous/synthetic TNP-470 158 EC proliferation Squalamine 159 EC proliferation Captopril 160 MMP-2, MMP-9 EC migration Combretastatin-A4 161 EC tubulin CP-547, 632 162 VEGFR-2 and bFGF kinases Vitaxin 163 a v b 3 integrin, EC apoptosis EMD121974 164 a v b 3 and a v b 5 integrin COL-3 83 MMP-2, -9, -14 MMPs Neovastat 165,166 MMP-2, -9, -12 MMPs, designed to avoid sheddases BMS-275291 54 MMP-1, -2, -3, -7, -9, -14 Bevacizumab 167 VEGF ited tumor growth and angiogenesis in vivo. Tumors overexpressing TIMP-3 failed to form a functional vasculature and had reduced pericyte recruitment.…”

Section: Timps As Potential Antiangiogenic Agentsmentioning

confidence: 99%

Metalloproteinases and their inhibitors in tumor angiogenesis

Handsley

Edwards

2005

Intl Journal of Cancer

263

211

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Angiogenesis is the process by which new blood vessels are formed from preexisting vasculature. It is an essential feature of the female reproductive cycle, embryonic development and wound repair. Angiogenesis has also been identified as a causal or contributing factor in several pathologies, including cancer, where it is a rate-limiting step during tumor progression. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, in particular the gelatinases and membrane-type 1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, unmasking of cryptic biologically relevant sites in ECM components, modulation of angiogenic factors and production of endogenous angiogenic inhibitors. This review brings together what is currently known about the functions of the MMPs and the closely related ADAM (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) families in angiogenesis and considers how this information might be useful in manipulation of the angiogenic process, with a view to constraining tumor progression. ' 2005 Wiley-Liss, Inc.Key words: metalloproteinase; tumor; angiogenesis; tissue inhibitor of metalloproteinases; protease; extracellular matrix Angiogenesis is an essential feature of several physiologic processes such as the developmental growth of organs, wound healing and the female reproductive cycle. 1 It is also particularly significant in cancer progression, being a crucial step in the transition of a tumor from a hyperplastic but contained in situ state to a malignant phenotype. 2,3 To allow its growth beyond a certain critical size, a solid avascular tumor must develop its own blood supply in order to meet its growing metabolic requirements. 1 Vascularization of a tumor also provides a route for dissemination of the tumor cells to different sites around the body.Although angiogenesis appears to be the primary form of tumor vascularization, the malignant cells of a tumor can gain access to a blood supply through other means, such as via tumor-induced vasculogenesis, in which bone marrow-derived precursor endothelial cells contribute to the formation of tumor vessels. 4,5 Vasculogenic mimicry is another form of vessel formation that has been reported in certain tumor types, such as aggressive human uveal melanomas, prostate and breast tumors. [6][7][8] In these cases, networks of tumor cell-lined vascular channels were identified within the tumors. Finally, vessel co-option, implemented by tumor cells as a temporary means of gaining access to a blood supply, involves the tumor cells growing around and thus co-opting existing host vessels to form an initially well-vascularized tumor. 9 This review will highlight new insigh...

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“…Some of these inhibitors are effective either as native full-length proteins or as proteolytic fragments [2]. This is the case for thrombospondins (TSP) 1 and 2, for which the mechanisms leading to inhibition of angiogenesis have been extensively studied and characterized [4]. Short sequences present in the N-terminal domain, especially in the thrombospondin type 1 repeats (TSR1), are released by ADAMTS-1 [5] and inhibit angiogenesis by interacting with the CD36 scavenger receptor [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity

Dubail¹,

Kesteloot²,

Deroanne³

et al. 2010

Cell. Mol. Life Sci.

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ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ADAMTS-2 is also able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. Dephosphorylation of Erk1/2 and MLC largely precedes the ADAMTS-2 induced morphological alterations. In 3-D culture models, ADAMTS-2 strongly reduced branching of capillarylike structures formed by endothelial cells and their long-term maintenance and inhibited vessels formation in embryoid bodies (EB). Growth and vascularization of tumors formed in nude mice by HEK 293-EBNA cells expressing ADAMTS-2 were drastically reduced. A similar anti-tumoral activity was observed when using cells expressing recombinant deleted forms of ADAMTS-2, including catalytically inactive enzyme. Nucleolin, a nuclear protein also found to be associated with the cell membrane, was identified as a potential receptor mediating the antiangiogenic properties of ADAMTS-2.

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Thrombospondins 1 and 2 function as inhibitors of angiogenesis

Cited by 271 publications

References 59 publications

Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers

Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers

Metalloproteinases and their inhibitors in tumor angiogenesis

ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity

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