S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells

Sayo Suzuki,Akito Nishimuta,Yasuko Yamayoshi,Yusuke Tanigawara

doi:10.1186/1477-5956-9-76

Sayo Suzuki, Akito Nishimuta + Show 2 more

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https://doi.org/10.1186/1477-5956-9-76

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Journal: Proteome science	Publication Date: Dec 1, 2011
Citations: 59	License type: cc-by

Affiliation: Keio University, Keio University Hospital

Abstract

BackgroundIndividual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. The objective of our study was to find candidate protein markers for tumor sensitivity to L-OHP from intracellular proteins of human colorectal cancer (CRC) cell lines. We performed expression difference mapping (EDM) analysis of whole cell lysates from 11 human CRC cell lines with different sensitivities to L-OHP by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and identified a candidate protein by liquid chromatography/mass spectrometry ion trap time-of-flight (LCMS-IT-TOF).ResultsOf the qualified mass peaks obtained by EDM analysis, 41 proteins were differentially expressed in 11 human colorectal cancer cell lines. Among these proteins, the peak intensity of 11.1 kDa protein was strongly correlated with the L-OHP sensitivity (50% inhibitory concentrations) (P < 0.001, R2 = 0.80). We identified this protein as Protein S100-A10 (S100A10) by MS/MS ion search using LCMS-IT-TOF. We verified its differential expression and the correlation between S100A10 protein expression levels in drug-untreated CRC cells and their L-OHP sensitivities by Western blot analyses. In addition, S100A10 protein expression levels were not correlated with sensitivity to 5-fluorouracil, suggesting that S100A10 is more specific to L-OHP than to 5-fluorouracil in CRC cells. S100A10 was detected in cell culture supernatant, suggesting secretion out of cells.ConclusionsBy proteomic approaches including SELDI technology, we have demonstrated that intracellular S100A10 protein expression levels in drug-untreated CRC cells differ according to cell lines and are significantly correlated with sensitivity of CRC cells to L-OHP exposure. Our findings provide a new clue to searching predictive markers of the response to L-OHP, suggesting that S100A10 is expected to be one of the candidate protein markers.

Highlights

Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable
Of the qualified mass peaks obtained by expression difference mapping (EDM) analysis, 41 proteins were differentially expressed in 11 human colorectal cancer cell lines (Figure 1A)
Correlation between S100A10 protein expression levels and sensitivity to L-OHP or 5-fluorouracil (5-FU) To confirm the results of candidate search study by SELDI-TOF MS analysis, we investigated the relationship between the sensitivity to L-OHP and S100A10 protein expression levels quantified by Western blot densitometry in 7 cell lines, which were used in the candidate search study, as the index data set

Summary

Introduction

Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. The objective of our study was to find candidate protein markers for tumor sensitivity to L-OHP from intracellular proteins of human colorectal cancer (CRC) cell lines. Genomic polymorphisms participating in nucleotide excision repair pathways, such as excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) and xeroderma pigmentosum group D (XPD, known as ERCC2), and the glutathione-S-transferase family of isozymes in detoxification pathways are considered potential predictors of clinical outcomes in patients given L-OHP-based chemotherapy [6,7,8,9]. How to predict the clinical response of CRC to L-OHP-based chemotherapy remains unclear [10]

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