Relationships between chemotaxis, chemotactic modulators, and cyclic nucleotide levels in tumor cells.
Like many freely moving cells, Walker 256 carcinosarcoma cells respond to chemotactic stimuli. Since cyclic nucleotides are involved in the chemotaxis of other cells, we have examined the action of several nucleosides and nucleotides as chemoattractants and as modulators of tumor cell movement. We have also studied the effect of chemoattractants and prostaglandins on intracellular cyclic nucleotide levels and the effect of prostaglandins as modulators of chemotaxis. Of the agents studied, only the cyclic nucleotides and prostaglandins were found to modulate cellular motility. Neither cyclic adenosine 3':5'-monophosphate (cAMP) nor cyclic guanosine 3':5'-monophosphate (cGMP) was a chemoattractant, but cGMP and N6,O2'-dibutyryl cyclic guanosine 3':5'-monophosphate at low concentrations (approximately 10(-10) M to 10(-8) M) enhanced chemotaxis by 80 +/- 15%, and both cAMP and N6,O2-dibutyryl cyclic adenosine 3':5'-monophosphate had an inhibitory effect at concentrations greater than 10(-6) M. Chemotaxis was suppressed by 21 to 100% in media depleted of Ca2+ and/or Mg2+, but in the presence of 10(-8) M cGMP, there was partial recovery of the chemotactic response. In response to chemotactic stimulation, there was a 28 to 60% rise in intracellular cAMP within 30 sec. This returned to basal levels within 2 min. Intracellular cGMP levels became elevated approximately 3- to 3.5-fold after this time. Incubation of cells with prostaglandins A1 and F2 alpha stimulated chemotaxis at lower concentrations (10(-7) and 10(-9) M, respectively) and resulted in elevation of cGMP, while incubation with prostaglandin E2 resulted in inhibition of chemotaxis and a rise in cAMP levels.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D011454:Prostaglandins A / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats
D002630:Chemotactic Factors; D011454:Prostaglandins A; D011458:Prostaglandins E; D011460:Prostaglandins F; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D015237:Dinoprost; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone; C100573:prostaglandin A1