title: Reversible abnormal nonadherence to glass and responsiveness to chemoattractants of leukocytes from patients with advanced cancer.
abstract: Whereas leukocytes from patients with early cancer usually show leukocyte adherence inhibition (LAI) to the sensitizing cancer extract, leukocytes from patients with advanced cancer seldom do. The chemoattractant-induced LAI response was studied to determine whether the abnormal response by leukocytes from patients with advanced cancer was related to changes in sensitivity to chemoattractants. Authentic chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine,  chemotactic fragment of the fifth component of complement, and leukotriene B4 (LTB4) at optimum concentrations induced about 28-31% of adherent leukocytes to become nonadherent, these leukocytes being from either controls or patients with early breast cancer. However, chemoattractants induced no increased nonadherence of adherent leukocytes from patients with advanced breast cancer. In the control tubes, nonadherent cells for patients with advanced cancer were already increased by about 38% and were slightly greater than the chemoattractant-induced increased of nonadherent cells for control subjects or patients with early cancer. When the intracellular cyclic AMP of the cells were raised transiently, the nonadherent cells in the control tubes for patients with advanced cancer decreased by about 38% compared to 8% for control subjects and 13% for patients with early cancer. When nonadherence was returned to control levels, about 46% of adherent cells from patients with advanced cancer became nonadherent to chemoattractants or to the sensitizing cancer extract. Normal leukocytes, preexposed to  chemoattractants, had increased nonadherence and did not respond to the same or other chemoattractants, imitating the state of leukocytes from patients with advanced cancer. However, if the cells were washed and intracellular cyclic AMP raised, nonadherent cells returned to normal levels in the control tubes and showed increased nonadherence with a repeat LTB4 exposure. The increased nonadherence of leukocytes from patients with advanced cancer as well as the refractoriness to chemoattractants was highly suggestive of in vivo activation of leukocytes possibly because of exposure to chemoattractant-like factors, generated by leukocyte-tumor antigen interactions.
mesh_terms: D001943:Breast Neoplasms / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D006801:Humans; D007957:Leukocyte Adherence Inhibition Test; D007962:Leukocytes / Q000502:physiology*; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009367:Neoplasm Staging; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D014020:Tissue Extracts / Q000494:pharmacology
chemical_list: D002630:Chemotactic Factors; D014020:Tissue Extracts; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine