Expression Profiling Using a CDNA Array and Immunohistochemistry for the Extracellular Matrix Genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in Colorectal Carcinoma Progression and Dissemination

Overview

Journal ScientificWorldJournal

Publisher Wiley

Specialty Biology

Date 2014 Apr 17

PMID 24737953

Citations 10

Authors

Suzana Angelica Silva Lustosa

Luciano de Souza Viana

Renato Jose Affonso Jr

Sandra Regina Morini Silva

Marcos Vinicius Araujo Denadai

Silvia Regina Caminada de Toledo

Indhira Dias Oliveira

Delcio Matos

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry tissue microarray methods were performed in samples from the primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5 genes were overexpressed in tumors with lymph node and distant metastasis (III/IV-stage tumors compared with I/II tumors). The MMP-2 gene showed significant overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a significant expression correlation with EGFR epithelial marker. The overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in mucinous and villous adenocarcinoma type tumors, respectively. The epithelial marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9 and ITGA-3 expression.

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References

Hoos A, Cordon-Cardo C . Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations. Lab Invest. 2001; 81(10):1331-8. DOI: 10.1038/labinvest.3780347. View

Chu D, Zhao Z, Zhou Y, Li Y, Li J, Zheng J . Matrix metalloproteinase-9 is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol. 2011; 19(1):318-25. DOI: 10.1245/s10434-011-1686-3. View

Bertucci F, Salas S, Eysteries S, Nasser V, Finetti P, Ginestier C . Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene. 2004; 23(7):1377-91. DOI: 10.1038/sj.onc.1207262. View

de Souza Viana L, Affonso Jr R, Silva S, Denadai M, Matos D, De Souza C . Relationship between the expression of the extracellular matrix genes SPARC, SPP1, FN1, ITGA5 and ITGAV and clinicopathological parameters of tumor progression and colorectal cancer dissemination. Oncology. 2012; 84(2):81-91. DOI: 10.1159/000343436. View

Raeder S, Utheim T, Utheim O, Nicolaissen B, Roald B, Cai Y . Effects of organ culture and Optisol-GS storage on structural integrity, phenotypes, and apoptosis in cultured corneal epithelium. Invest Ophthalmol Vis Sci. 2007; 48(12):5484-93. DOI: 10.1167/iovs.07-0494. View

Pupa S, Menard S, Forti S, Tagliabue E . New insights into the role of extracellular matrix during tumor onset and progression. J Cell Physiol. 2002; 192(3):259-67. DOI: 10.1002/jcp.10142. View

Bendardaf R, Buhmeida A, Hilska M, Laato M, Syrjanen S, Syrjanen K . MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients. Cancer Invest. 2009; 28(1):38-43. DOI: 10.3109/07357900802672761. View

Stallmach A, von Lampe B, Matthes H, Bornhoft G, Riecken E . Diminished expression of integrin adhesion molecules on human colonic epithelial cells during the benign to malign tumour transformation. Gut. 1992; 33(3):342-6. PMC: 1373824. DOI: 10.1136/gut.33.3.342. View

Arnaout M, Goodman S, Xiong J . Structure and mechanics of integrin-based cell adhesion. Curr Opin Cell Biol. 2007; 19(5):495-507. PMC: 2443699. DOI: 10.1016/j.ceb.2007.08.002. View

10.

Jinka R, Kapoor R, Sistla P, Raj T, Pande G . Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers. Int J Cell Biol. 2012; 2012:219196. PMC: 3259478. DOI: 10.1155/2012/219196. View

11.

Desgrosellier J, Cheresh D . Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2009; 10(1):9-22. PMC: 4383089. DOI: 10.1038/nrc2748. View

12.

Zucker S, Vacirca J . Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004; 23(1-2):101-17. DOI: 10.1023/a:1025867130437. View

13.

Murnane M, Cai J, Shuja S, McAneny D, Klepeis V, Willett J . Active MMP-2 effectively identifies the presence of colorectal cancer. Int J Cancer. 2009; 125(12):2893-902. PMC: 2775048. DOI: 10.1002/ijc.24682. View

14.

Ghilardi G, Biondi M, Mangoni J, Leviti S, DeMonti M, Guagnellini E . Matrix metalloproteinase-1 promoter polymorphism 1G/2G is correlated with colorectal cancer invasiveness. Clin Cancer Res. 2001; 7(8):2344-6. View

15.

Bianchi A, Gervasi M, Bakin A . Role of β5-integrin in epithelial-mesenchymal transition in response to TGF-β. Cell Cycle. 2010; 9(8):1647-59. DOI: 10.4161/cc.9.8.11517. View

16.

Pesta M, Topolcan O, Holubec Jr L, Rupert K, cerna M, Holubec L . Clinicopathological assessment and quantitative estimation of the matrix metalloproteinases MMP-2 and MMP-7 and the inhibitors TIMP-1 and TIMP-2 in colorectal carcinoma tissue samples. Anticancer Res. 2007; 27(4A):1863-7. View

17.

Streit M, Schmidt R, Hilgenfeld R, Thiel E, Kreuser E . Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. J Mol Med (Berl). 1996; 74(5):253-68. DOI: 10.1007/BF00196578. View

18.

Nicoloso M, Spizzo R, Shimizu M, Rossi S, Calin G . MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009; 9(4):293-302. DOI: 10.1038/nrc2619. View

19.

Borg T . It's the matrix! ECM, proteases, and cancer. Am J Pathol. 2004; 164(4):1141-2. PMC: 1615333. DOI: 10.1016/S0002-9440(10)63201-4. View

20.

Oshima T, Kunisaki C, Yoshihara K, Yamada R, Yamamoto N, Sato T . Clinicopathological significance of the gene expression of matrix metalloproteinases and reversion-inducing cysteine-rich protein with Kazal motifs in patients with colorectal cancer: MMP-2 gene expression is a useful predictor of liver metastasis.... Oncol Rep. 2008; 19(5):1285-91. View