Parathyroid Hormone-Related Protein Suppression Against Melanoma Progression

Parathyroid Hormone-Related Protein Suppression Against Melanoma Progression

Researchers from the Royal Victoria Hospital, Montréal, Canada, recently published a study in the Endocrine journal showing that the role of the Parathyroid Hormone-Related Protein (PTHrP) in melanoma invasion and metastasis is closely associated with tumour progression.

The action mechanism of this molecule was studied through in vitro inactivation of the Pthrp gene in human melanoma cell lines, to understand if inactivating the Pthrp gene could be beneficial to brake melanoma progression.

Pthrp-ablated cells showed rounder morphology, decreased motility and a significant reduction in the invasion capacity compared with nonablated A375 cells. PTHrP peptide and culture medium from the melanoma cell line restored, partially, the invasive phenotype of the genetic-deficient cells. Furthermore, the team observed that Pthrp ablation decreased actin polymerization, matrix metallopeptidase 9 expression and focal adhesion kinase phosphorylation.

Dao Chao Huang, lead author of the study, and his team also studied this mechanism in vivo. Green fluorescent protein-transduced ablated and nonablated melanoma cells (which can emit green fluorescent light) were injected intracardially or subcutaneously into mice to study proliferation and multi-organ metastasis. Five days after injection, dissemination of infected Pthrp-ablated cells to the lungs was reduced by 85% and dissemination to the liver was reduced by 50%, when compared with the nonablated controls.
The number of metastatic lesions was much lower in mice injected with Pthrp-ablated melanoma cells, with 45% of the mice injected with the ablated cell lines surviving for a 7-week period, compared with 15% of mice injected with the nonablated cells. Also, mice injected with the normal melanoma cells and treated with a blocking anti-PTHrP monoclonal antibody (to mimick gene ablation) saw their tumour size decreased by more than 80% over 4 weeks, with a significantly improved survival of over 8 months.
These results, show that PTHrP has a major role in melanoma invasion and metastasis. Thus, suppressing PTHrP may be crucial against melanoma progression.

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