Decreased expression of the low density lipoprotein receptor-related protein/α2-macroglobulin receptor in invasive cell clones derived from human prostate and breast tumor cells

Ravi K. Kancha, Mark E. Stearns, M. Mahmood Hussain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

The importance of receptors involved in the clearance of proteases and protease/inhibitor complexes in tumor invasion is unknown. We studied the expression of the low density lipoprotein receptor-related protein/α2-macroglobulin receptor (LRP/α2-MR), the major receptor involved in the clearance of protease/inhibitor complexes, in invasive and noninvasive subclones derived from tumor cells. The receptor activity was 2- to 3-fold lower in invasive subclones compared to noninvasive subclones derived from human prostate PC-3 and DU 145 and melanoma A2058 cells. The receptor activity was decreased in breast cancer (MCF-10A) cells transfected with mutated Ha-ras compared to nontransfected cells. Furthermore, invasive cells derived from ras-transfected MCF-10A cells expressed lower levels of receptor compared to their non-invasive counterparts. These studies indicate a correlation between invasive phenotype and low receptor expression in different tumor cells. Experiments were performed to understand two possible mechanisms (decreased transcription of the receptor and increased transcription of an inhibitory protein) for the decreased cell-surface expression of the receptor in invasive cells. The decreased expression in invasive subclones was due to 2- to 3-fold lower levels of LRP/α2-MR mRNA in all cells. In invasive PC-3 subclones, but not in DU 145, A2058, and MCF-10A subclones, 2-fold higher levels of the 39 kDa receptor-associated protein (an inhibitor of the receptor) mRNA were observed. These studies showed that the decreased expression of LRP/α2-MR activity in invasive subclones was generally correlated with the decreased steady-state mRNA levels of the receptor. The decreased expression of the LRP/α2-MR may increase cell-surface urokinase activity and help tumor cells during invasion.

Original languageEnglish
Pages (from-to)365-372
Number of pages8
JournalOncology Research
Volume6
Issue number8
Publication statusPublished - 1994
Externally publishedYes

Keywords

  • Ha-ras
  • LDL receptor-related protein/α-macroglobulin receptor
  • protease/inhibitor complexes
  • tumor cell invasion

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