Osteopontin Overexpression Induced Tumor Progression and Chemoresistance to Oxaliplatin through Induction of Stem-Like Properties in Human Colorectal Cancer

Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. The poor prognosis of colorectal cancer patients is due to development of chemoresistance and cancer metastasis. Recently osteopontin (OPN) has been associated with stem-like properties in colorectal cancer. This study further examined the clinicopathological significance of OPN in CRC and its effect on chemoresistance and transcription of stem cell markers. We examined the transcription level of OPN in 84 CRC patients and correlated the expression with their clinicopathological parameters. The associations of OPN overexpression with transcription of stem cell markers and response to chemotherapy in DLD1-OPN overexpressing clones and CRC patients were also investigated. Our results showed that OPN was significantly overexpressed in CRC, and its overexpression correlated with tumor stage and poor prognosis. Overexpression of CRC induced OCT4 and SOX2 expressionin vitroand correlated with SOX2 overexpression in CRC patients. In addition, DLD1-OPN overexpressing cells showed enhanced ability to survive upon oxaliplatin treatment, and OPN expression was higher in CRC patients who were resistant to oxaliplatin-involved chemotherapy treatment. Thus, CRC cells overexpressing OPN demonstrated stem-like properties and OPN inhibition is a potential therapeutic approach to combat CRC progression and chemoresistance.

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Abstract 5210: Over-expression of cancer stem cell markers predicted poor prognosis in colorectal cancer

10.1158/1538-7445.am2011-5210 ◽

2011 ◽

Author(s):

Mayumi Ozawa ◽

Yasushi Ichikawa ◽

Takashi Oshima ◽

Akihisa Kondo ◽

Kenichi Nakazawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Poor Prognosis ◽

Stem Cell Markers ◽

Cell Markers ◽

Cancer Stem Cell Markers ◽

Over Expression

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Faculty Opinions recommendation of ILK Expression in Colorectal Cancer Is Associated with EMT, Cancer Stem Cell Markers and Chemoresistance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733254991.793550602 ◽

2018 ◽

Author(s):

Avri Ben-Ze'ev

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Stem Cell Markers ◽

Cell Markers ◽

Cancer Stem Cell Markers

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The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽

10.1159/000519913 ◽

2022 ◽

pp. 1-10

Author(s):

Cheng Yang ◽

Na Xie ◽

Zhifei Luo ◽

Xiling Ruan ◽

Yixin Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Mrna Level ◽

Normal Mucosa ◽

Tnm Stage ◽

Expression Levels ◽

Normal Tissues

Introduction: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). Methods: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. Results: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. Conclusion: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

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Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer

British Journal of Cancer ◽

10.1038/sj.bjc.6605762 ◽

2010 ◽

Vol 103 (3) ◽

pp. 382-390 ◽

Cited By ~ 167

Author(s):

A Lugli ◽

G Iezzi ◽

I Hostettler ◽

M G Muraro ◽

V Mele ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Prognostic Impact ◽

Stem Cell Markers ◽

Cell Markers ◽

Cancer Stem Cell Markers

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Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts

Scientific Reports ◽

10.1038/s41598-019-49853-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Laura L. Stafman ◽

Adele P. Williams ◽

Raoud Marayati ◽

Jamie M. Aye ◽

Hooper R. Markert ◽

...

Keyword(s):

Stem Cell ◽

Tumor Cell ◽

Cell Survival ◽

Cell Lines ◽

Human Condition ◽

Migration And Invasion ◽

Stem Cell Markers ◽

Cell Markers ◽

Cycle Arrest

Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

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