The Role of MMP7 and Its Cross-talk with the FAS/FASL System During the Acquisition of Chemoresistance to Oxaliplatin

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Mar 7

PMID 19266094

Citations 44

Authors

Vanessa Almendro

Elisabet Ametller

Susana Garcia-Recio

Olga Collazo

Ignasi Casas

Josep M Auge

Joan Maurel

Pedro Gascon

Affiliations

Soon will be listed here.

Abstract

Background: The efficacy of oxaliplatin in cancer chemotherapy is limited by the development of drug resistance. MMP7 has been related to the loss of tumor cell response to cytotoxic agents although the exact mechanism is not fully understood. Moreover, MMP7 is an independent prognosis factor for survival in patients with colorectal cancer. The aim of the present study was to analyze the role of MMP7 and its cross-talk with the Fas/FasL system during the acquisition of oxaliplatin resistance in colon cancer cells.

Principal Findings: For this purpose we have developed three different oxaliplatin-resistant cell lines (RHT29, RHCT116 p53(+/+), RHCT116 p53(-/-)) from the parental HT29, HCT116 p53(+/+) and HCT116 p53(-/-) colon cancer cells. MMP7 basal expression was higher in the resistant compared to the parental cell lines. MMP7 was also upregulated by oxaliplatin in both HT29 (p53 mutant) and RHCT116 p53(-/-) but not in the RHCT116 p53(+/+). Inhibition of MMP by 1,10-phenantroline monohydrate or siRNA of MMP7 restores cell sensitivity to oxaliplatin-induced apoptosis in both HT29 and RHCT116 p53(-/-) but not in the RHCT116 p53(+/+). Some of these effects are caused by alterations in Fas receptor. Fas is upregulated by oxaliplatin in colon cancer cells, however the RHT29 cells treated with oxaliplatin showed a 3.8-fold lower Fas expression at the cell surface than the HT29 cells. Decrease of Fas at the plasma membrane seems to be caused by MMP7 since its inhibition restores Fas levels. Moreover, functional analysis of Fas demonstrates that this receptor was less potent in inducing apoptosis in RHT29 cells and that its activation induces MAPK signaling in resistant cells.

Conclusions: Taking together, these results suggest that MMP7 is related to the acquisition of oxaliplatin-resistance and that its inhibition restores drug sensitivity by increasing Fas receptor. Furthermore, Fas undergoes a change in its functionality in oxaliplatin-resistant cells inducing survival pathways instead of apoptotic signals.

Citing Articles

Longitudinal Circulating Tumor Cell Collection, Culture, and Characterization in Pancreatic Adenocarcinomas.

Xiao J, Mukherji R, Sidarous G, Suguru S, Noel M, Weinberg B Cancers (Basel). 2025; 17(3).

PMID: 39941724 PMC: 11815863. DOI: 10.3390/cancers17030355.

A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer.

Shadnoush M, Momenan M, Seidel V, Tierling S, Fatemi N, Nazemalhosseini-Mojarad E Pharmacol Rep. 2024; 77(1):103-123.

PMID: 39304638 DOI: 10.1007/s43440-024-00652-y.

Improved Drug-Response Prediction Model of APC Mutant Colon Cancer Patient-Derived Organoids for Precision Medicine.

Shin Y, Jo E, Oh Y, Kim D, Hyun S, Yu A Cancers (Basel). 2023; 15(23).

PMID: 38067236 PMC: 10705195. DOI: 10.3390/cancers15235531.

Clinical Significance of MMP7 Levels in Colorectal Cancer Patients Receiving FOLFOX4 Chemotherapy Treatment.

Zhou Y, Wang L, Zhou F Int J Gen Med. 2023; 16:2671-2678.

PMID: 37398512 PMC: 10312346. DOI: 10.2147/IJGM.S416363.

Identification of co-regulated genes associated with doxorubicin resistance in the MCF-7/ADR cancer cell line.

Miri A, Gharechahi J, Samiei Mosleh I, Sharifi K, Jajarmi V Front Oncol. 2023; 13:1135836.

PMID: 37397367 PMC: 10311417. DOI: 10.3389/fonc.2023.1135836.

References

Yang A, Fan F, Camp E, Van Buren G, Liu W, Somcio R . Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res. 2006; 12(14 Pt 1):4147-53. DOI: 10.1158/1078-0432.CCR-06-0038. View

Osorio L, Aguilar-Santelises M, de Santiago A, Hachiya T, Mellstedt H, Jondal M . Increased serum levels of soluble Fas in progressive B-CLL. Eur J Haematol. 2001; 66(5):342-6. DOI: 10.1034/j.1600-0609.2001.066005342.x. View

Liu K, McDuffie E, Abrams S . Exposure of human primary colon carcinoma cells to anti-Fas interactions influences the emergence of pre-existing Fas-resistant metastatic subpopulations. J Immunol. 2003; 171(8):4164-74. DOI: 10.4049/jimmunol.171.8.4164. View

Nonomura N, Nishimura K, Ono Y, Fukui T, Harada Y, Takaha N . Soluble Fas in serum from patients with renal cell carcinoma. Urology. 2000; 55(1):151-5. DOI: 10.1016/s0090-4295(99)00379-9. View

Giambernardi T, Grant G, Taylor G, Hay R, Maher V, McCormick J . Overview of matrix metalloproteinase expression in cultured human cells. Matrix Biol. 1998; 16(8):483-96. DOI: 10.1016/s0945-053x(98)90019-1. View

Muller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M . p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J Exp Med. 1998; 188(11):2033-45. PMC: 2212386. DOI: 10.1084/jem.188.11.2033. View

Fingleton B, Vargo-Gogola T, Crawford H, Matrisian L . Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia. 2002; 3(6):459-68. PMC: 1506562. DOI: 10.1038/sj.neo.7900190. View

Chan R, Muller W, Matrisian L . The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. Cancer Res. 1998; 58(23):5500-6. View

Witty J, McDonnell S, Newell K, Cannon P, Navre M, Tressler R . Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo. Cancer Res. 1994; 54(17):4805-12. View

10.

Egeblad M, Werb Z . New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002; 2(3):161-74. DOI: 10.1038/nrc745. View

11.

Lee K, Feig C, Tchikov V, Schickel R, Hallas C, Schutze S . The role of receptor internalization in CD95 signaling. EMBO J. 2006; 25(5):1009-23. PMC: 1409734. DOI: 10.1038/sj.emboj.7601016. View

12.

Ferrer B, Bermudo R, Thomson T, Nayach I, Soler M, Sanchez M . Paraffin-embedded cell line microarray (PECLIMA): development and validation of a high-throughput method for antigen profiling of cell lines. Pathobiology. 2005; 72(5):225-32. DOI: 10.1159/000089416. View

13.

Vargo-Gogola T, Fingleton B, Crawford H, Matrisian L . Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo. Cancer Res. 2002; 62(19):5559-63. View

14.

Mizutani Y, Hongo F, Sato N, Ogawa O, Yoshida O, Miki T . Significance of serum soluble Fas ligand in patients with bladder carcinoma. Cancer. 2001; 92(2):287-93. DOI: 10.1002/1097-0142(20010715)92:2<287::aid-cncr1321>3.0.co;2-4. View

15.

Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y . Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood). 2005; 231(1):20-7. DOI: 10.1177/153537020623100103. View

16.

Khong H, Restifo N . Natural selection of tumor variants in the generation of "tumor escape" phenotypes. Nat Immunol. 2002; 3(11):999-1005. PMC: 1508168. DOI: 10.1038/ni1102-999. View

17.

Chen C, Chen L, Tsou T, Pan W, Kuo C, Liu J . Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil. Br J Cancer. 2007; 97(3):334-44. PMC: 2360324. DOI: 10.1038/sj.bjc.6603866. View

18.

Yamamoto H, Adachi Y, Itoh F, Iku S, Matsuno K, Kusano M . Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res. 1999; 59(14):3313-6. View

19.

Wang W, Chen P, Wang H, Liang W, Su Y . Matrix metalloproteinase-7 increases resistance to Fas-mediated apoptosis and is a poor prognostic factor of patients with colorectal carcinoma. Carcinogenesis. 2006; 27(5):1113-20. DOI: 10.1093/carcin/bgi351. View

20.

Goldberg R, Sargent D, Morton R, Fuchs C, Ramanathan R, Williamson S . A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2003; 22(1):23-30. DOI: 10.1200/JCO.2004.09.046. View