Total Knockdown of LMW-PTP in MDA-MB-231 Cells Reduces Osteoclastogenesis

Anticancer Res. 2017 Dec;37(12):6671-6677. doi: 10.21873/anticanres.12125.

Abstract

Background: Low molecular weight protein tyrosine phosphatase (LMW-PTP) has been related to tumorigenesis, having both oncogenic and anti-oncogenic roles. The differential roles of its main active isoforms (fast and slow) may account for these discrepancies. The fast isoform has been described to be involved in the bone-metastatic process, although knockdown of the slow isoform was recently reported to reduce osteoclastogenesis. We aimed to study the influence of LMW-PTP isoforms on osteoclast differentiation.

Materials and methods: Osteoclast precursors (RAW 264.7) were cultured with conditioned medium from MDA-MB-231 breast cancer cells with total knockdown of LMW-PTP and with knockdown of the slow isoform of LMW-PTP. Tartarate-resistant acid phosphatase (TRAP) staining and quantification were performed to assess osteoclast differentiation.

Results: Total knockdown of LMW-PTP, but not of slow LMW-PTP significantly reduced osteoclast differentiation of RAW 264.7 cells.

Conclusion: We suggest that total LMW-PTP increases osteoclastic differentiation, albeit not at the expense of the slow isoform.

Keywords: LMW-PTP; Low molecular weight protein tyrosine phosphatase; MDA-MB-231; bone metastasis; breast cancer.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Line, Tumor
  • Culture Media, Conditioned / pharmacology
  • Female
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mice
  • Osteoclasts / metabolism*
  • Osteogenesis / genetics*
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA Interference*

Substances

  • Culture Media, Conditioned
  • Isoenzymes
  • Proto-Oncogene Proteins
  • ACP1 protein, human
  • Protein Tyrosine Phosphatases