Low-density lipoprotein receptor-related protein 1b impairs cellular proliferation in human cell lines

Low-density lipoprotein (LDL) receptor-related protein 1b (LRP1b) is one of three very large receptors of the LDL receptor family, several members of which have been implicated in the pathogenesis of atherosclerosis. LRP1b was discovered during studies of lung cancer cell lines, where alterations of the receptor were frequently found and LRP1b was therefore postulated as a putative tumor suppressor. LRP1b is expressed in human brain, thyroid gland, skeletal muscle, and to a lesser amount in testis. Previously, we demonstrated binding of LRP1b to circulating ligands like very low density lipoprotein, high density lipoprotein, and fibrinogen. We generated an expression vector containing the full length 13.800 bp murine LRP1b cDNA for overexpression (OE) of the receptor in LRP1b-negative lung cancer cell lines (A427, A549) and used siRNA for silencing in LRP1b-positive lung cancer cells (Calu-1). Cellular proliferation was analyzed using a BrdU incorporation ELISA and anchorage-independent growth using a soft agar colony formation assay, respectively. Consistent with the postulated tumor suppressor function, overexpression of mLRP1b in A427 and A549 cells significantly reduced both cellular proliferation and anchorage-independent growth compared to mock-transfected control cells. Conversely, siRNA mediated knockdown of hLRP1b in Calu-1 lung cancer cells led to a significant increase in cellular proliferation compared to scrambled (SCR)-siRNA treated control cells (Fig 1). ![Figure][1] Figure 1 Our findings demonstrate that overexpression of full length LRP1b leads to impaired cellular proliferation, while LRP1b knockdown has the opposite effect. These experiments may help in unraveling the largely unknown physiological role of LRP1b and its potential functions in cancer and atherosclerosis. [1]: pending:yes