PDGF-D/PDGF-ββ receptor-regulated chemotaxis of malignant mesothelioma cells

Our plain-English summary of PDGF-D/PDGF-ββ receptor-regulated chemotaxis of malignant mesothelioma cells, by A. Okada, T. Yaguchi, T. Kanno, et al (Cellular Physiology and Biochemistry, 2012).

The study

• Authors: A. Okada, T. Yaguchi, T. Kanno, A. Gotoh, T. Nakano, T. Nishizaki
• Journal: Cellular Physiology and Biochemistry
• Published: 2012;29(1-2):241-50
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background/aims: Our earlier study suggested that platelet-derived growth factor (PDGF)- ββ receptor regulates chemotaxis of human malignant mesothelioma cells such as MSTO-211H, NCIH-2052, NCIH-2452, and NCIH-28 cells, but not non-malignant Met5A cells. The present study was designed to gain further insight into the PDGF-ββ receptor signals underlying the chemotaxis.

Methods: PDGF-D secreted from cells, activation of Akt and ERK, and cell migration were monitored for cells with and without knocking-down PDGF-ββ receptor.

Results: FBS significantly stimulated PDGF-D secretion from malignant mesothelioma cells, but not Met5A cells. PDGF-D activated Akt and ERK in both the non-malignant and malignant cells. PDGF-D significantly facilitated migration of malignant mesothelioma cells, but not Met5A cells, with the extent varying among the cell types. The facilitatory action of PDGF-D was clearly prevented by knocking-down PDGF-ββ receptor or inhibitors of PI3 kinase, PDK1, Akt, Rac1, ROCK, and MEK.

Conclusion: The results of the present study indicate that PDGF-D promotes malignant mesothelioma cell chemotaxis through PDGF-ββ receptor signaling pathways along a PI3 kinase/PDK1/Akt/Rac1/ROCK axis and relevant to ERK activation.

Copyright © 2012 S. Karger AG, Basel.

In plain English

This was a laboratory study of human cells grown in culture. It did not study asbestos exposure or patients. The authors used four purchased malignant mesothelioma cell lines (MSTO-211H, NCIH-2052, NCIH-2452 and NCIH-28) and one non-malignant mesothelial cell line (Met5A). They examined how a growth factor called PDGF-D affects chemotaxis, the directed movement of the cells. Adding fetal bovine serum (FBS) raised the amount of PDGF-D the malignant cells released to 1.5 to 3 times basal levels, depending on cell type. The increase for Met5A cells was not statistically significant. PDGF-D increased migration of the malignant cells, to differing degrees, but not of Met5A cells. This effect was abolished when the PDGF-ββ receptor was silenced, and it was blocked by inhibitors of PI3 kinase, PDK1, Akt, Rac1, ROCK and MEK1. PDGF-D activated the signaling proteins Akt and ERK1 in both malignant and non-malignant cells. The authors concluded that PDGF-D activates PDGF-ββ receptors in an autocrine manner, meaning the cells respond to a factor they release themselves.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory (in vitro) cell-culture experiment
• Who was studied: Four human malignant mesothelioma cell lines (MSTO-211H, NCIH-2052, NCIH-2452, NCIH-28) and one human non-malignant mesothelial cell line (Met5A), purchased from the American Type Culture Collection; no human subjects
• Exposure: No asbestos exposure was studied. Cells were treated with 1% FBS and with PDGF-D (4 ng in the migration assay). Some cells had the PDGF-ββ receptor silenced by siRNA, and some were given signaling inhibitors.
• Main results:
  • In the four malignant mesothelioma cell lines, FBS significantly increased extracellular PDGF-D to 1.5 to 3 times basal levels, depending on cell type.
  • In non-malignant Met5A cells, FBS increased extracellular PDGF-D, but not significantly.
  • PDGF-D facilitated migration of the malignant mesothelioma cells, with potency differing among cell types.
  • PDGF-D did not facilitate migration of non-malignant Met5A cells.
  • In malignant cells, the migration-promoting effect of PDGF-D was abolished by knocking down the PDGF-ββ receptor.
  • PDGF-D increased activated (phosphorylated) Akt and ERK1 in all the non-malignant and malignant cells. These effects were inhibited by knocking down the PDGF-ββ receptor.
  • In malignant cells, PDGF-D-induced migration was prevented by inhibitors of PI3 kinase, PDK1, Akt, Rac1 and ROCK.
  • In malignant cells, PDGF-D-induced migration was also significantly suppressed by the MEK1 inhibitor PD98059.
• The authors' conclusion: The authors concluded that PDGF-D activates PDGF-ββ receptors in an autocrine manner. They stated that this involves the PI3 kinase/PDK1/Akt/Rac1/ROCK and MAPK signaling pathways and promotes malignant mesothelioma cell chemotaxis.

Topics

Medical terms in this study, explained in our Lexicon: Platelet-Derived Growth Factor (PDGF), Malignant Mesothelioma.

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