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Calcitonin induces stem cell-like phenotype in prostate cancer cells.
- Source :
-
Endocrine-related cancer [Endocr Relat Cancer] 2019 Nov; Vol. 26 (11), pp. 815-828. - Publication Year :
- 2019
-
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.
- Subjects :
- AC133 Antigen
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Collagen metabolism
Humans
Hyaluronan Receptors
Male
Mice, Inbred BALB C
Mice, Nude
Neoplastic Stem Cells pathology
Phenotype
Prostatic Neoplasms pathology
Receptors, Calcitonin metabolism
Wound Healing
Calcitonin metabolism
Neoplastic Stem Cells metabolism
Prostatic Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1479-6821
- Volume :
- 26
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Endocrine-related cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31561211
- Full Text :
- https://doi.org/10.1530/ERC-19-0333