Chemotherapy enhances endothelial cell reactivity to platelets.
Recent studies indicate that chemotherapy is a cause for thrombosis in breast cancer patients. We performed experiments to determine whether the enhanced thrombosis was due, in part, to an effect of chemotherapy on endothelial cell reactivity. Heparinized blood samples were obtained from stage II breast cancer patients receiving monthly adjuvant chemotherapy consisting of cyclophosphamide, epirubicin and 5-fluorouracil. Cultured human endothelial cells were incubated with the plasmas for 2 h, and then the reactivity of the endothelial cells to normal donor platelets was determined isotopically. Endothelial cell reactivity was increased when the endothelial cells were incubated with the post-chemotherapy plasmas. The plasma effect persisted after the chemotherapy drugs were cleared from the circulation, but this plasma effect was abolished when the plasmas were heat-inactivated. Furthermore, the increase in endothelial cell reactivity correlated with the level of interleukin-1 present in the post-chemotherapy plasmas. Finally, the increased endothelial cell reactivity was inhibited by the GRGDS peptide, or by an antibody to the endothelial cell vitronectin receptor. These observations suggest that chemotherapeutic drugs alter endothelial cell reactivity to platelets by inducing the release of interleukin-1 which, in turn, facilitates adhesion molecule expression on the endothelial cell surface. If so, these observations provide a possible explanation for one mechanism which may contribute to the thrombogenic effect seen in breast cancer patients undergoing chemotherapy.
Bertomeu
M C
MC
McMaster University, Department of Pathology, Hamilton, Ontario, Canada.
Gallo
S
S
Lauri
D
D
Levine
M N
MN
Orr
F W
FW
Buchanan
M R
MR
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001792:Blood Platelets / Q000502:physiology*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D010973:Platelet Adhesiveness; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000096:biosynthesis; D013927:Thrombosis / Q000139:chemically induced*
D000970:Antineoplastic Agents; D007375:Interleukin-1; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic