The Role of Colorectal Cancer Stem Cells in Metastatic Disease and Therapeutic Response

Anderson, Eric; Hessman, Crystal J.; Levin, Trevor G.; Monroe, Marcus M.; Wong, Melissa H.

doi:10.3390/cancers3010319

Cited by 64 publications

(54 citation statements)

References 88 publications

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“…There is increasing evidence that CSCs may play an important role in tumor disease progression (21)(22)(23)(24)(25). The CD133 membrane glycoprotein is considered as a valid CSC marker (26-31) that has previously been shown to be capable of identifying a cancerinitiating subpopulation in EpCAM-positive solid tumors.…”

Section: T-cell Activation In Malignant Ascites Samplesmentioning

confidence: 99%

Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM × Anti-CD3)

et al. 2012

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Patients with malignant ascites secondary to primary carcinomas benefit from intraperitoneal therapy with the trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3). Here, we report the analysis of peritoneal fluid samples from 258 patients with malignant ascites randomized to catumaxomab or control groups to investigate the molecular effects of catumaxomab treatment. In the catumaxomab group, tumor cell numbers and peritoneal levels of VEGF decreased, whereas the activation status of CD4+ and CD8+ T-cell populations increased more than two-fold after treatment. Notably, CD133+/EpCAM+ cancer stem cells vanished from the catumaxomab samples but not from the control samples. In vitro investigations indicated that catumaxomab eliminated tumor cells in a manner associated with release of proinflammatory Th1 cytokines. Together, our findings show that catumaxomab therapy activates peritoneal T cells and eliminates EpCAM+ tumor cells, establishing a molecular and cellular basis to understand in vivo efficacy within the immunosuppressed malignant ascites tissue microenvironment. Cancer Res; 72(1); 24–32. ©2011 AACR.

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Section: T-cell Activation In Malignant Ascites Samplesmentioning

confidence: 99%

Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM × Anti-CD3)

et al. 2012

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“…The CRC-derived CICs have been demonstrated previously to be the key tumor compartment in establishing this neoplastic disease in animal models (11,12). Although different immunotherapies have been considered in relation to CRC tumor, there is little information available concerning immunologically important properties of the CRC-derived initiating cells.…”

mentioning

confidence: 99%

Human NK Cells Selective Targeting of Colon Cancer–Initiating Cells: A Role for Natural Cytotoxicity Receptors and MHC Class I Molecules

Tallerico

Todaro

Franco

et al. 2013

The Journal of Immunology

227

145

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Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the “differentiated” cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma–derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the “differentiated” tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors.

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“…Traditional therapy targets rapidly dividing tumor cells for the maximum reduction of tumor; however, the tumor-maintaining cells (CSCs) are less susceptible to chemotherapy 22) and can migrate to other sites. 23) Therefore, targeting CSCs is an important strategy to cure metastatic cancer, including CRC, which is resistant to conventional therapy.…”

Section: Discussionmentioning

confidence: 99%

Profilin 2 promotes migration, invasion, and stemness of HT29 human colorectal cancer stem cells

Kim

Lee

Han

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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We investigated the role of profilin 2 in the stemness, migration, and invasion of HT29 cancer stem cells (CSCs). Increased and decreased levels of profilin 2 significantly enhanced and suppressed the self-renewal, migration, and invasion ability of HT29 CSCs, respectively. Moreover, profilin 2 directly regulated the expression of stemness markers (CD133, SOX2, and β-catenin) and epithelial mesenchymal transition (EMT) markers (E-cadherin and snail). CD133 and β-catenin were up-regulated by overexpression of profilin 2 and down-regulated by depletion of profilin 2. SOX2 was decreased by profilin 2 depletion. E-cadherin was not influenced by profilin 2-overexpression but increased by profilin 2-knockdown. The expression of snail was suppressed by profilin 2-knockdown. We speculated that stemness and the EMT are closely linked through profilin 2-related pathways. Therefore, this study indicates that profilin 2 affects the metastatic potential and stemness of colorectal CSCs by regulating EMT-and stemness-related proteins.

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The Role of Colorectal Cancer Stem Cells in Metastatic Disease and Therapeutic Response

Cited by 64 publications

References 88 publications

Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM × Anti-CD3)

Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM × Anti-CD3)

Human NK Cells Selective Targeting of Colon Cancer–Initiating Cells: A Role for Natural Cytotoxicity Receptors and MHC Class I Molecules

Profilin 2 promotes migration, invasion, and stemness of HT29 human colorectal cancer stem cells

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