Calcitonin induces stem cell-like phenotype in prostate cancer cells

Abstract

Stem cell-like-cancer cells are key drivers of tumor growth, metastasis, and relapse of cancer following remission. Prostate stem cell-like cancer cells isolated from human prostate cancer (PC) biopsies express CD44+/α2β1 hi/CD133+ cell surface markers and can self-renew in vitro. Expression of calcitonin (CT) and its receptor (CTR) is frequently elevated in PCs and activation of CT-CTR axis in non-invasive PC cells induces an invasive phenotype. We investigated whether CT-CTR autocrine axis induces stem cell-like phenotype in two PC cell lines. CT-CTR axis in these cell lines was activated by enforced expression of CTR. The cells were then examined for the changes in the expression of CD44 and CD133, collagen adherence, tumorigenic, metastatic and repopulating characteristics. The activation of CT-CTR axis led to a large increase in adherence to collagen and a remarkable increase of CD44 and CD133 in PC-3 and LNCaP cells. This was accompanied by a strong increase in tumorigenic, metastatic and repopulation properties of PC cells. However, the mutation of CTR-C PDZ-binding site in CTR almost abolished CTR-mediated increases in stem cell-like characteristics of PC cells. These results support an important role for CT-CTR axis in the progression of PC from localized cancer to an aggressive form, and a majority of proinvasive CTR actions may be mediated through its interaction with its partner protein at the PDZ-binding site. These results suggest that CT/CTR can serve as a valuable target to prevent the generation of stem-like PC cells.

The Mangrove-Derived Diterpenoid Diaporthe B Inhibits the Stemness and Increases the Efficacy of Docetaxel in Prostate Cancer PC-3 Cells

“…The expansion of CSCs after chemotherapy has been identified as an important factor responsible for acquired therapeutic drug resistance. 13,14,26…”

“…The expansion of CSCs after chemotherapy has been identified as an important factor responsible for acquired therapeutic drug resistance. 13,14,26 To investigate whether CSCs are involved in the resistance of PC-3 cells to docetaxel, we determined tumor sphere formation, which is one of the characteristics of CSC 27 in PC-3 and docetaxel-resistant PC-3 cells. In contrast to a monolayer of cells grown in adherent cultures (Figure 2C), in serum containing medium, PC-3 (Figure 2D) and the docetaxel-resistant PC-3 (Figure 2E) cells formed nonadherent spheroid cell clusters when they were cultured with the serum-free medium in ultralow attachment plates.…”

Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development

“…When the CT-CTR pathway was induced in PC-3 and LNCaP cells, the adherence to collagen and the expression of CD133 and CD44 were significantly enhanced. The researchers also observed a potentiated tumorigenic and metastatic ability and an enhanced self-generation (Aldahish et al, 2019). One can conclude that the CT-CTR couple should be considered as a crucial target when it comes to developing therapies that hamper PCa development.…”

Zinc finger protein‑like 1 is a novel neuroendocrine biomarker for prostate cancer

“…LNCaP and LNCaP-C4 cells were obtained from the American Type Culture Collection (ATCC). PC3-CTR cells were derived by stable expression of CTR in PC-3 cells as previously described (20)(21)(22). To ensure that the expression of CTR did not alter the characteristics of PC-3 parental cells, PC-3CTR cell line was authenticated by STR profiling of PC3-CTR and PC-3 cells at Johns Hopkins Cell line authentication core facility (Baltimore, USA).…”