Initial exposed phosphatidylserine levels correlate with cellular response to cytotoxic drugs.
Phosphatidylserine's (PS) membranal distribution is associated with an expanding variety of biological processes. We studied the relevance of preliminarily exposed membranal PS levels to cellular effects of cytotoxic agents. PBL of normal controls (n = 18) and patients with doxorubicin-treated breast carcinoma (n = 27) or 5'-fluorouracil-treated colorectal cancer (n = 32) were assayed before and after drug infusion. Membranal expression levels of PS, adhesion molecules (CD18, CD11a-c, CD63) and Fas-R of leukocyte subtypes were assessed by flow cytometer. Statistical analysis was implemented. Our results demonstrate external expression of PS on all leukocyte subpopulations despite non-apoptotic light scatter characteristics. Several distinct features were observed of which the more prominent were: leukocyte subtypes each display characteristic PS levels; cancer patients' PBL display higher preliminary PS levels than normal controls in all cell groups; and existence of negative correlations between initial membranal PS levels and drug-induced changes in its expression. Our findings underscore the complex involvement of PS in PBL apoptosis and possibly drug resistance.
Drucker
Liat
L
Oncogenetic Laboratory, Sapir Medical Center, Meir Hospital, Kfar Sava, Israel. druckerl@clalit.org.il
Ciobotaro
Pnina
P
Kimchi
Oded
O
Tohami
Tali
T
Yarkoni
Shai
S
Radnay
Judith
J
Shapira
Hava
H
Lishner
Michael
M
D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000648:ultrastructure; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*
D000970:Antineoplastic Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D010718:Phosphatidylserines