Upregulated phospholipase D2 expression and activity is related to the metastatic properties of melanoma

Oncol Lett. 2022 May;23(5):140. doi: 10.3892/ol.2022.13260. Epub 2022 Mar 9.

Abstract

The incidence rates of melanoma have increased steadily in recent decades and nearly 25% of the patients diagnosed with early-stage melanoma will eventually develop metastasis, for which there is currently no fully effective treatment. The link between phospholipases and tumors has been studied extensively, particularly in breast and colon cancers. With the aim of finding new biomarkers and therapeutic options for melanoma, the expression of different phospholipases was assessed in 17 distinct cell lines in the present study, demonstrating that phospholipase D2 (PLD2) is upregulated in metastatic melanoma as compared to normal skin melanocytes. These results were corroborated by immunofluorescence and lipase activity assays. Upregulation of PLD2 expression and increased lipase activity were observed in metastatic melanoma relative to normal skin melanocytes. So far, the implication of PLD2 activity in melanoma malignancies has remained elusive. To the best of our knowledge, the present study was the first to demonstrate that the overexpression of PLD2 enhances lipase activity, and its effect to increase the proliferation, migration and invasion capacity of melanoma cells was assessed with XTT and Transwell assays. In addition, silencing of PLD2 in melanoma cells reduced the metastatic potential of these cells. The present study provided evidence that PLD2 is involved in melanoma malignancy and in particular, in its metastatic potential, and established a basis for future studies evaluating PLD2 blockade as a therapeutic strategy to manage this condition.

Keywords: cell invasion; cell migration; cell proliferation; enzyme activity; lipidomics; melanoma; metastasis; phosphatidylcholine; phospholipase D2; phospholipases.

Grants and funding

This study was supported by grants from the University of the Basque Country/EHU (grant no. GIU17/066) and Ministerio de Economía y Competividad MINECO-ONCOFINDER of the Spanish Government (grant no. RTC.2015-3693-1).