Procathepsin D and cytokines influence the proliferation of lung cancer cells.

Enzymatically inactive procathepsin D (pCD) has been established as an important factor in the development of lung cancer. In addition to serving as a growth factor, pCD is also involved in communication between cancer cells and surrounding cells. In the present investigation, a possible combination of autocrine and paracrine actions of pCD was investigated. pCD initiated secretion of interleukin (IL)-4, IL-8, IL-10 and IL-13 from lung cancer cells. These cytokines participated in the proliferation of the cancer cells, as demonstrated both by adding the cytokines and by inhibition using specific anti-cytokine antibodies. Using several clones of lung cancer cells differing in production of activation peptide, the pCD/cytokine cooperation and action was shown to be dependent on pCD secretion. Further proof that pCD is one of the key molecules involved in cancer development is presented.