Colon Cancer: Organoids, Microenvironment and Vitamin D

Our group studies human colon cancer, which is a major neoplasia in terms of incidence and mortality worldwide and the most frequent neoplasia in Spain if both genders are jointly considered. In the past, by using established human colon carcinoma cell lines and animal models, we made seminal contributions in the field of Wnt signaling and characterized in-depth the antitumor effects of vitamin D in this pathology.

Nowadays, we use primary cultures of fibroblasts and stem cell-derived organoids established from healthy and tumor tissue of colon cancer patients to investigate the role of the Wnt/β-catenin pathway, the contribution of the tumor microenvironment, and the antitumor action of vitamin D in this neoplasia.

Our group is now mainly dedicated to two novel research lines:

1) The effects of vitamin D on cancer-associated fibroblasts, which are the main cellular component of the tumor microenvironment and play a crucial role in colon tumorigenesis.

2) The effects of vitamin D and Wnt factors on the gene expression, proliferation, and phenotype of colon organoids, which are 3D-structures generated by normal or tumor stem cells that are more similar to the tissue-of-origin and reproduce the in vivo situation better than 2D-cultures of immortalized cell lines.

Our objectives are:

a) To in-depth characterize vitamin D action on cancer-associated fibroblasts and on their relation with carcinoma cells and other cells of tumor stroma.

b) To identify and study Wnt and vitamin D target genes in cancer-associated fibroblasts and colon organoids.

c) To analyze vitamin D effect on cell phenotype and cell differentiation and on Wnt/β-catenin signaling in colon normal and tumor organoids.

d) To study the response of organoids to antitumor drugs currently used for the treatment of colon cancer patients and to other drugs still in development and its putative modulation by vitamin D.

e) To continue the elucidation of the antagonism exerted by vitamin D on Wnt/β-catenin signaling in colon cancer.

We collaborate with other cancer research groups to establish synergies in mechanisms, processes and techniques that may contribute to the advance of our research. We offer our experience in the establishment of next-generation cellular models (organoids and primary cultures of cancer-associated fibroblasts derived from patient biopsies) and our knowledge of Wnt/β-catenin signaling, which is crucial in colon cancer and other neoplasias.


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