MDA-MB-231 Breast Cancer Cells Overexpressing Single VEGF Isoforms Display Distinct Colonisation Characteristics

Overview

Journal Br J Cancer

Specialty Oncology

Date 2015 Jul 22

PMID 26196186

Citations 12

Authors

Melanie Di Benedetto

Aurore Toullec

Helene Buteau-Lozano

Mohamed Abdelkarim

Sophie Vacher

Guillaume Velasco

Monique Christofari

Marc Pocard

Ivan Bieche

Martine Perrot-Applanat

Affiliations

Soon will be listed here.

Abstract

Background: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has important roles in angiogenesis. Our knowledge of the significance of VEGF isoforms in human cancer remains incomplete.

Methods: Bioluminescence imaging and transcriptomic analysis were used to study the colonisation capacity of the human breast cancer cells MDA-MB-231 controlling or overexpressing the VEGF165 or VEGF189 isoform (named cV-B, V165-B and V189-B, respectively) in nude mice.

Results: When injected into the bloodstream, V189-B cells induced less metastasis in the lungs and bone than V165-B and cV-B control cells, consistent with longer survival of these mice and delay in tumour uptake in the mice injected with a V189-B clone. Histological analysis confirmed that there were less αSMA-positive cells in the lungs of the mice injected with V189-B. In vitro V189-B cells decreased both cell invasion and survival. Using transcriptomic analysis, we identified a subset of 18 genes expressed differentially between V189 and V165 cell lines and in 120 human breast tumours. V165 was associated with poor prognosis, whereas V189 was not, suggesting a complex regulation by VEGF isoforms. Our results showed a negative correlation between the expression pattern of VEGF189 and the levels of expression of seven genes that influence metastasis.

Conclusion: Our findings provide the first evidence that VEGF isoforms have different effects on breast cancer cell line colonisation in vivo.

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References

Herve M, Buteau-Lozano H, Mourah S, Calvo F, Perrot-Applanat M . VEGF189 stimulates endothelial cells proliferation and migration in vitro and up-regulates the expression of Flk-1/KDR mRNA. Exp Cell Res. 2005; 309(1):24-31. DOI: 10.1016/j.yexcr.2005.05.022. View

Tomii Y, Yamazaki H, Sawa N, Ohnishi Y, Kamochi J, Tokunaga T . Unique properties of 189 amino acid isoform of vascular endothelial growth factor in tumorigenesis. Int J Oncol. 2002; 21(6):1251-7. View

Jacobsen J, Grankvist K, Rasmuson T, Ljungberg B . Different isoform patterns for vascular endothelial growth factor between clear cell and papillary renal cell carcinoma. BJU Int. 2006; 97(5):1102-8. DOI: 10.1111/j.1464-410X.2006.06138.x. View

Steeg P . Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006; 12(8):895-904. DOI: 10.1038/nm1469. View

Gupta G, Massague J . Cancer metastasis: building a framework. Cell. 2006; 127(4):679-95. DOI: 10.1016/j.cell.2006.11.001. View

Lee T, Seng S, Sekine M, Hinton C, Fu Y, Avraham H . Vascular endothelial growth factor mediates intracrine survival in human breast carcinoma cells through internally expressed VEGFR1/FLT1. PLoS Med. 2007; 4(6):e186. PMC: 1885450. DOI: 10.1371/journal.pmed.0040186. View

Fukasawa M, Matsushita A, Korc M . Neuropilin-1 interacts with integrin beta1 and modulates pancreatic cancer cell growth, survival and invasion. Cancer Biol Ther. 2007; 6(8):1173-80. DOI: 10.4161/cbt.6.8.4363. View

Herve M, Buteau-Lozano H, Vassy R, Bieche I, Velasco G, Pla M . Overexpression of vascular endothelial growth factor 189 in breast cancer cells leads to delayed tumor uptake with dilated intratumoral vessels. Am J Pathol. 2007; 172(1):167-78. PMC: 2189622. DOI: 10.2353/ajpath.2008.070181. View

Tozer G, Akerman S, Cross N, Barber P, Bjorndahl M, Greco O . Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors. Cancer Res. 2008; 68(7):2301-11. DOI: 10.1158/0008-5472.CAN-07-2011. View

10.

El-Mabhouh A, Nation P, Kaddoura A, Mercer J . Unexpected preferential brain metastases with a human breast tumor cell line MDA-MB-231 in BALB/c nude mice. Vet Pathol. 2008; 45(6):941-4. DOI: 10.1354/vp.45-6-941. View

11.

Abdelkarim M, Guenin E, Sainte-Catherine O, Vintonenko N, Peyri N, Perret G . New symmetrically esterified m-bromobenzyl non-aminobisphosphonates inhibited breast cancer growth and metastases. PLoS One. 2009; 4(3):e4685. PMC: 2650402. DOI: 10.1371/journal.pone.0004685. View

12.

Matsuyama M, Chijiwa T, Inoue Y, Abe Y, Nishi M, Miyazaki N . Alternative splicing variant of vascular endothelial growth factor-A is a critical prognostic factor in non-small cell lung cancer. Oncol Rep. 2009; 22(6):1407-13. DOI: 10.3892/or_00000582. View

13.

Workman P, Aboagye E, Balkwill F, Balmain A, Bruder G, Chaplin D . Guidelines for the welfare and use of animals in cancer research. Br J Cancer. 2010; 102(11):1555-77. PMC: 2883160. DOI: 10.1038/sj.bjc.6605642. View

14.

Bos P, Nguyen D, Massague J . Modeling metastasis in the mouse. Curr Opin Pharmacol. 2010; 10(5):571-7. PMC: 2952835. DOI: 10.1016/j.coph.2010.06.003. View

15.

Zhang H, Scott P, Morbidelli L, Peak S, Moore J, Turley H . The 121 amino acid isoform of vascular endothelial growth factor is more strongly tumorigenic than other splice variants in vivo. Br J Cancer. 2000; 83(1):63-8. PMC: 2374542. DOI: 10.1054/bjoc.2000.1279. View

16.

Irizarry R, Hobbs B, Collin F, Beazer-Barclay Y, Antonellis K, Scherf U . Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003; 4(2):249-64. DOI: 10.1093/biostatistics/4.2.249. View

17.

Bachelder R, Lipscomb E, Lin X, Wendt M, Chadborn N, Eickholt B . Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Cancer Res. 2003; 63(17):5230-3. View

18.

Mackie E, Chiquet-Ehrismann R, Pearson C, Inaguma Y, Taya K, Kawarada Y . Tenascin is a stromal marker for epithelial malignancy in the mammary gland. Proc Natl Acad Sci U S A. 1987; 84(13):4621-5. PMC: 305142. DOI: 10.1073/pnas.84.13.4621. View

19.

Tischer E, Mitchell R, Hartman T, Silva M, GOSPODAROWICZ D, Fiddes J . The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991; 266(18):11947-54. View

20.

Soker S, Vlodavsky I, Neufeld G . The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. J Biol Chem. 1992; 267(9):6093-8. View