Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 5/2012

01-10-2012 | Research Article

Vascular density and endothelial cell expression of integrin alpha v beta 3 and E-selectin in murine tumours

Authors: Johanne Seguin, Céline Nicolazzi, Nathalie Mignet, Daniel Scherman, Guy G. Chabot

Published in: Tumor Biology | Issue 5/2012

Login to get access

Abstract

The endothelial cell adhesion molecules, including the integrin alpha v beta 3 (αvβ3) and E-selectin, are involved in the process of angiogenesis required for tumour growth, cell migration and metastasis. The purpose of this study was to assess and compare widely used tumour models to select the ones most suitable for angiogenesis research. Fifteen murine tumours were selected including melanoma (B16), colon (C26, C38, C51), mammary (MA13, MA16, MA16/Adr, MA17, MA17/Adr, MA25, MA44), pancreatic (PO2, PO3), Glasgow osteogenic sarcoma (GOS) and Lewis lung carcinoma (LLC). The tumour vascular density, assessed using the platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) immunostaining, revealed that B16 melanoma was poorly vascularized (<5 %), whereas the colon and mammary tumours were well vascularized (5–15 %). The most vascularized tumours (>15 %) were the pancreatic tumours (PO2 and PO3), the sarcoma (GOS) and the lung tumour (LLC). The integrin αvβ3 and E-selectin, evaluated by immunohistology, showed that 7/15 tumours expressed the αvβ3 integrin which was homogeneously distributed on all tumour sections (B16, C26, MA17/Adr, MA25, MA44, PO2, LLC). E-selectin was expressed in 4/15 tumours and its expression was restricted to the tumour periphery. Only 2/15 tumours (B16 and C26) were shown to express both integrin αvβ3 and E-selectin. In conclusion, these data not only contribute to a better understanding of the tumour biology of murine tumours but can also guide the choice of appropriate models for antiangiogenic therapy, for selective drug delivery to tumours and the validation of tumour imaging modalities targeting these endothelial cell adhesion molecules.
Literature
1.
2.
Nussenbaum F, Herman IM. Tumor angiogenesis: insights and innovations. J Oncol. 2010;2010:132641.
3.
Bischoff J. Cell adhesion and angiogenesis. J Clin Invest. 1997;100:S37–9.PubMed
4.
O. I, Otvos L, Kieber-Emmons T, Blaszczyk-Thurin M. Role of SA-Le(a) and E-selectin in metastasis assessed with peptide antagonist. Peptides. 2002;23:999–1010.
5.
Hosotani R, Kawaguchi M, Masui T, Koshiba T, Ida J, Fujimoto K, Wada M, Doi R, Imamura M. Expression of integrin alphaVbeta3 in pancreatic carcinoma: relation to MMP-2 activation and lymph node metastasis. Pancreas. 2002;25:e30–5.CrossRefPubMed
6.
Langley RR, Russell J, Eppihimer MJ, Alexander SJ, Gerritsen M, Specian RD, Granger DN. Quantification of murine endothelial cell adhesion molecules in solid tumors. Am J Physiol. 1999;277:H1156–66.PubMed
7.
Varner JA, Cheresh DA. Tumor angiogenesis and the role of vascular cell integrin alpha v beta 3. Important Adv Oncol. 1996;1996:69-87.
8.
Kraling BM, Razon MJ, Boon LM, Zurakowski D, Seachord C, Darveau RP, Mulliken JB, Corless CL, Bischoff J. E-selectin is present in proliferating endothelial cells in human hemangiomas. Am J Pathol. 1996;148:1181–91.PubMedPubMedCentral
9.
Friedlander M, Theesfeld CL, Sugita M, Fruttiger M, Thomas MA, Chang S, Cheresh DA. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proc Natl Acad Sci U S A. 1996;93:9764–9.CrossRefPubMedPubMedCentral
10.
11.
Max R, Gerritsen RR, Nooijen PT, Goodman SL, Sutter A, Keilholz U, Ruiter DJ, De Waal RM. Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor-associated vessels of human carcinomas. Int J Cancer. 1997;71:320–4.CrossRefPubMed
12.
Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G, Cheresh DA. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994;79:1157–64.CrossRefPubMed
13.
Eliceiri BP, Cheresh DA. The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest. 1999;103:1227–30.CrossRefPubMedPubMedCentral
14.
15.
Haviv YS, Curiel DT. Conditional gene targeting for cancer gene therapy. Adv Drug Deliv Rev. 2001;53:135–54.CrossRefPubMed
16.
Nguyen M, Eilber FR, Defrees S. Novel synthetic analogs of sialyl Lewis X can inhibit angiogenesis in vitro and in vivo. Biochem Biophys Res Commun. 1996;228:716–23.CrossRefPubMed
17.
Yasuda M, Shimizu S, Ohhinata K, Naito S, Tokuyama S, Mori Y, Kiuchi Y, Yamamoto T. Differential roles of ICAM-1 and E-selectin in polymorphonuclear leukocyte-induced angiogenesis. Am J Physiol Cell Physiol. 2002;282:C917–25.CrossRefPubMed
18.
Mannori G, Santoro D, Carter L, Corless C, Nelson RM, Bevilacqua MP. Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin. Am J Pathol. 1997;151:233–43.PubMedPubMedCentral
19.
Vonlaufen A, Wiedle G, Borisch B, Birrer S, Luder P, Imhof BA. Integrin alpha(v)beta(3) expression in colon carcinoma correlates with survival. Mod Pathol. 2001;14:1126–32.CrossRefPubMed
20.
Polin L, Corbett TH, Roberts BJ, Lawson AJ, Leopold III WR, White K, Kushner J, Hazeldine S, Moore R, Rake J, Horwitz JP. Transplantable syngeneic rodent tumors: Solid tumors of mice. In: Teicher BA, editor. Tumors models in cancer research, Cancer Drug Discovery and Development. New York: Springer Science & Business Media LLC; 2011. p. 43–78.CrossRef
21.
Fidler IJ. Biological behavior of malignant melanoma cells correlated to their survival in vivo. Cancer Res. 1975;35:218–24.PubMed
22.
Corbett TH, Griswold Jr DP, Roberts BJ, Peckham JC, Schabel Jr FM. Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 1975;35:2434–9.PubMed
23.
Corbett TH, Griswold Jr DP, Roberts BJ, Peckham JC, Schabel Jr FM. Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer. 1977;40:2660–80.CrossRefPubMed
24.
Corbett TH, Griswold Jr DP, Roberts BJ, Peckham JC, Schabel Jr FM. Biology and therapeutic response of a mouse mammary adenocarcinoma (16/C) and its potential as a model for surgical adjuvant chemotherapy. Cancer Treat Rep. 1978;62:1471–88.PubMed
25.
Schabel Jr FM, Skipper HE, Trader MW, Laster Jr WR, Griswold Jr DP, Corbett TH. Establishment of cross-resistance profiles for new agents. Cancer Treat Rep. 1983;67:905–22.PubMed
26.
Liang J, Moore RE, Moher ED, Munroe JE, Al-awar RS, Hay DA, Varie DL, Zhang TY, Aikins JA, Martinelli MJ, Shih C, Ray JE, Gibson LL, Vasudevan V, Polin L, White K, Kushner J, Simpson C, Pugh S, Corbett TH. Cryptophycins-309, 249 and other cryptophycin analogs: preclinical efficacy studies with mouse and human tumors. Invest New Drugs. 2005;23:213–24.CrossRefPubMed
27.
Corbett TH, Roberts BJ, Leopold WR, Peckham JC, Wilkoff LJ, Griswold Jr DP, Schabel Jr FM. Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice. Cancer Res. 1984;44:717–26.PubMed
28.
Glasgow LA, Crane Jr JL, Kern ER, Youngner JS. Antitumor activity of interferon against murine osteogenic sarcoma in vitro and in vivo. Cancer Treat Rep. 1978;62:1881–8.PubMed
29.
Bertram JS, Janik P. Establishment of a cloned line of Lewis Lung Carcinoma cells adapted to cell culture. Cancer Lett. 1980;11:63–73.CrossRefPubMed
30.
31.
Rofstad EK, Danielsen T. Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis. Br J Cancer. 1999;80:1697–707.CrossRefPubMedPubMedCentral
32.
Strohmeyer D. Pathophysiology of tumor angiogenesis and its relevance in renal cell cancer. Anticancer Res. 1999;19:1557–61.PubMed
33.
34.
Boles KS, Schmieder AH, Koch AW, Carano RA, Wu Y, Caruthers SD, Tong RK, Stawicki S, Hu G, Scott MJ, Zhang H, Reynolds BA, Wickline SA, Lanza GM. MR angiogenesis imaging with Robo4- vs. alphaVbeta3-targeted nanoparticles in a B16/F10 mouse melanoma model. FASEB J. 2010;24:4262–70.CrossRefPubMedPubMedCentral
35.
Felding-Habermann B, Fransvea E, O'Toole TE, Manzuk L, Faha B, Hensler M. Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastasis. 2002;19:427–36.CrossRefPubMed
36.
Desgrosellier JS, Barnes LA, Shields DJ, Huang M, Lau SK, Prevost N, Tarin D, Shattil SJ, Cheresh DA. An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Nat Med. 2009;15:1163–9.CrossRefPubMedPubMedCentral
37.
Nelson H, Ramsey PS, Donohue JH, Wold LE. Cell adhesion molecule expression within the microvasculature of human colorectal malignancies. Clin Immunol Immunopathol. 1994;72:129–36.CrossRefPubMed
38.
Fox SB, Turner GD, Gatter KC, Harris AL. The increased expression of adhesion molecules ICAM-3, E- and P-selectins on breast cancer endothelium. J Pathol. 1995;177:369–76.CrossRefPubMed
39.
Barthel SR, Gavino JD, Descheny L, Dimitroff CJ. Targeting selectins and selectin ligands in inflammation and cancer. Expert Opin Ther Targets. 2007;11:1473–91.CrossRefPubMedPubMedCentral
40.
Jubeli E, Moine L, Vergnaud-Gauduchon J, Barratt G. E-selectin as a target for drug delivery and molecular imaging. J Control Release. 2012;158:194–206.CrossRefPubMed
41.
Senger DR, Perruzzi CA, Streit M, Koteliansky VE, de Fougerolles AR, Detmar M. The alpha(1)beta(1) and alpha(2)beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am J Pathol. 2002;160:195–204.CrossRefPubMedPubMedCentral
42.
Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala-Dilke KM. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med. 2002;8:27–34.CrossRefPubMed
43.
44.
45.
Wesseling JG, Bosma PJ, Krasnykh V, Kashentseva EA, Blackwell JL, Reynolds PN, Li H, Parameshwar M, Vickers SM, Jaffee EM, Huibregtse K, Curiel DT, Dmitriev I. Improved gene transfer efficiency to primary and established human pancreatic carcinoma target cells via epidermal growth factor receptor and integrin-targeted adenoviral vectors. Gene Ther. 2001;8:969–76.CrossRefPubMed
46.
Hood JD, Bednarski M, Frausto R, Guccione S, Reisfeld RA, Xiang R, Cheresh DA. Tumor regression by targeted gene delivery to the neovasculature. Science. 2002;296:2404–7.CrossRefPubMed
47.
Spragg DD, Alford DR, Greferath R, Larsen CE, Lee KD, Gurtner GC, Cybulsky MI, Tosi PF, Nicolau C, Gimbrone Jr MA. Immunotargeting of liposomes to activated vascular endothelial cells: a strategy for site-selective delivery in the cardiovascular system. Proc Natl Acad Sci U S A. 1997;94:8795–800.CrossRefPubMedPubMedCentral
48.
Gutheil JC, Campbell TN, Pierce PR, Watkins JD, Huse WD, Bodkin DJ, Cheresh DA. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res. 2000;6:3056–61.PubMed
49.
Kumar CC, Malkowski M, Yin Z, Tanghetti E, Yaremko B, Nechuta T, Varner J, Liu M, Smith EM, Neustadt B, Presta M, Armstrong L. Inhibition of angiogenesis and tumor growth by SCH221153, a dual alpha(v)beta3 and alpha(v)beta5 integrin receptor antagonist. Cancer Res. 2001;61:2232–8.PubMed
50.
51.
Mas-Moruno C, Rechenmacher F, Kessler H. Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation. Anticancer Agents Med Chem. 2010;10:753–68.CrossRefPubMedPubMedCentral
52.
53.
Liu ZJ, Tian R, Li Y, An W, Zhuge Y, Livingstone AS, Velazquez OC. Inhibition of tumor angiogenesis and melanoma growth by targeting vascular E-selectin. Ann Surg. 2011;254:450–6.CrossRefPubMed
54.
55.
Bissery MC, Nguyen CH, Bisagni E, Vrignaud P, Lavelle F. Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzo-pyrido-indole: evaluation against solid tumors and leukemias in mice. Invest New Drugs. 1993;11:263–77.CrossRefPubMed
56.
Bissery MC, Guenard D, Gueritte-Voegelein F, Lavelle F. Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue. Cancer Res. 1991;51:4845–52.PubMed
57.
Corbett TH, Leopold WR, Dykes DJ, Roberts BJ, Griswold Jr DP, Schabel Jr FM. Toxicity and anticancer activity of a new triazine antifolate (NSC 127755). Cancer Res. 1982;42:1707–15.PubMed
58.
LoRusso PM, Demchik L, Foster B, Knight J, Bissery MC, Polin LM, Leopold III WR, Corbett TH. Preclinical antitumor activity of CI-994. Invest New Drugs. 1996;14:349–56.PubMed
59.
DeWys WD. Studies correlating the growth rate of a tumor and its metastases and providing evidence for tumor-related systemic growth-retarding factors. Cancer Res. 1972;32:374–9.PubMed
Metadata
Title
Vascular density and endothelial cell expression of integrin alpha v beta 3 and E-selectin in murine tumours
Authors
Johanne Seguin
Céline Nicolazzi
Nathalie Mignet
Daniel Scherman
Guy G. Chabot
Publication date
01-10-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0428-x

Other articles of this Issue 5/2012

Tumor Biology 5/2012 Go to the issue

Research Article

Opposite roles of LPA1 and LPA3 on cell motile and invasive activities of pancreatic cancer cells

Research Article

Cyclin D1 G870A polymorphism and lung cancer risk: a meta-analysis

Research Article

CpG ODN107 potentiates radiosensitivity of human glioma cells via TLR9-mediated NF-κB activation and NO production

Research Article

ADAM10 overexpression confers resistance to doxorubicin-induced apoptosis in hepatocellular carcinoma

Research Article

Mammalian Sulf1 RNA alternative splicing and its significance to tumour growth regulation

Research Article

The single nucleotide polymorphism g.1548A >G (K469E) of the ICAM-1 gene is associated with worse prognosis in non-small cell lung cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits