Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids

Cave, Donatella Delle; Hernando-Momblona, Xavier; Sevillano, Marta; Minchiotti, Gabriella; Lonardo, Enza

doi:10.7150/thno.54027

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2021; 11(12):5686-5699. doi:10.7150/thno.54027 This issue Cite

Research Paper

Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids

Donatella Delle Cave¹, Xavier Hernando-Momblona², Marta Sevillano², Gabriella Minchiotti¹, Enza Lonardo^1,2✉

1. Institute of Genetics and Biophysics'Adriano Buzzati-Traverso' (IGB), CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
2. Institute for Research in Biomedicine Barcelona (IRB), Barcelona, Spain.

Citation:

Cave DD, Hernando-Momblona X, Sevillano M, Minchiotti G, Lonardo E. Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids. Theranostics 2021; 11(12):5686-5699. doi:10.7150/thno.54027. https://www.thno.org/v11p5686.htm

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Abstract

Background: Colorectal cancer (CRC) is currently the third leading cause for cancer-related mortality. Cancer stem cells have been implicated in colorectal tumor growth, but their specific role in tumor biology, including metastasis, is still uncertain.

Methods: Increased expression of L1CAM, CXCR4 and NODAL was identified in tumor section of patients with CRC and in patients-derived-organoids (PDOs). The expression of L1CAM, CXCR4 and NODAL was evaluated using quantitative real-time PCR, western blotting, immunofluorescence, immunohistochemistry and flow cytometry. The effects of the L1CAM, CXCR4 and NODAL on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.

Results: We found that human colorectal cancer tissue contains cancer stem cells defined by L1CAM^high/CXCR4^high expression that is activated by Nodal in hypoxic microenvironment. This L1CAM^high/CXCR4^high population is tumorigenic, highly resistant to standard chemotherapy, and determines the metastatic phenotype of the individual tumor. Depletion of the L1CAM^high/CXCR4^high population drastically reduces the tumorigenic potential and the metastatic phenotype of colorectal tumors.

Conclusion: In conclusion, we demonstrated that a subpopulation of migrating L1CAM^high/CXCR4^high is essential for tumor progression. Together, these findings suggest that strategies aimed at modulating the Nodal signaling could have important clinical applications to inhibit colorectal cancer-derived metastasis.

Keywords: colorectal cancer (CRC), organoids, transforming growth factor (TGF)-β signaling, L1 cell adhesion molecule (L1CAM, CD171)

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APA

Cave, D.D., Hernando-Momblona, X., Sevillano, M., Minchiotti, G., Lonardo, E. (2021). Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids. Theranostics, 11(12), 5686-5699. https://doi.org/10.7150/thno.54027.

ACS

Cave, D.D.; Hernando-Momblona, X.; Sevillano, M.; Minchiotti, G.; Lonardo, E. Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids. Theranostics 2021, 11 (12), 5686-5699. DOI: 10.7150/thno.54027.

NLM

CSE

Cave DD, Hernando-Momblona X, Sevillano M, Minchiotti G, Lonardo E. 2021. Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids. Theranostics. 11(12):5686-5699.

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