Adhesion to 90K (Mac-2 BP) as a mechanism for lymphoma drug resistance in vivo.
A cell-adhesive protein of the human serum, 90K binds galactin-3, beta1-integrins, collagens, and fibronectin, and it is of importance in cell-cell and cell-extracellular matrix adhesion. Serum 90K levels in 137 patients with lymphoma were measured by enzyme-linked immunosorbent assay. Compared with healthy controls, pretreatment serum 90K levels in patients with lymphoma were elevated (P <.001). Of 97 patients who showed objective response to treatment, 20 (21%) had pretreatment 90K levels above the normal cutoff compared with 17 (53%) of 32 patients who did not respond (P =.002). When used as a plastic-immobilized substrate, 90K caused a significant reduction in chemotherapy-induced apoptosis of Jurkat T lymphoma cells. This finding could explain the lack of response in lymphoma patients with high 90K serum levels.
Fornarini
B
B
Department of Oncology and Neurosciences, University G. D'Annunzio Medical School, Chieti, Italy.
D'Ambrosio
C
C
Natoli
C
C
Tinari
N
N
Silingardi
V
V
Iacobelli
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D002448:Cell Adhesion / Q000502:physiology*; D003520:Cyclophosphamide / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D018432:Drug Resistance, Multiple; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D019169:Jurkat Cells; D008223:Lymphoma / Q000097:blood / Q000145:classification / Q000188:drug therapy*; D016393:Lymphoma, B-Cell / Q000097:blood / Q000188:drug therapy; D016399:Lymphoma, T-Cell / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D016326:Extracellular Matrix Proteins
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D003520:Cyclophosphamide; D004317:Doxorubicin; D006023:Glycoproteins; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins