PDGF receptors are expressed in the stromal compartment in most common solid tumors. Inhibition of stromally expressed PDGF receptors in a rat colon carcinoma model reduces the tumor interstitial fluid pressure and increases tumor transcapillary transport. Increased Taxol tumor uptake was also demonstrated. Arterial restenosis, which involves PDGF stimulation of smooth muscle cells, is a frequent complication after surgical treatment of atherosclerosis. In a rat model of restenosis we observed initial beneficial effects of PDGF antagonists but also found that restenosis re-occurs after drug removal.
Results are pending.
The details and functional importance of these interactions is largely unknown. This suggests that in some instances PTPs modulate rather than turn off RTKs. To what extent this contributes to RTK signaling specificity will be investigated by analyzing PDGF receptor signaling in cell lines that lack or overexpress individual PTPs. Efforts to identify the molecular mechanisms underlying this phenomenon are ongoing. Most receptor-like PTPs are still orphan receptors.