TY - JOUR
T1 - Characterization of tumor-induced platelet aggregation
T2 - The role of immunorelated GPIb and GPIIb IIIa expression by MCF-7 breast cancer cells
AU - Oleksowicz, Leslie
AU - Mrowiec, Zbigniew
AU - Schwartz, Edward
AU - Khorshidi, Manoochehr
AU - Dutcher, Janice P.
AU - Puszkin, Elena
N1 - Funding Information:
This work was supported in part by the American Cancer Society Clinical Oncology Career Development Award (CD-93-52, L.O.), and Cancer Center Core Grant P30CA1330-21 by the National Cancer Institute. We are grateful to Dr. Fritz Herz, who provided the MCF-7 cells and assistance in our early studies. We thank Margie De Leon Femandez for her excellent technical assistance.
PY - 1995/8/1
Y1 - 1995/8/1
N2 - Tumor cell induced platelet aggregation is thought to be an early step in the metastatic process. Here we show that platelet aggregation induced by MCF-7 cells is mediated, in part, through an ADP-dependent mechanism based on inhibition of aggregation by pretreatment of the tumor cells with apyrase and the identification of ADP in tumor cell-free supernatants by HPLC. By applying immunocytochemical and flow cytometric techniques, we demonstrate that platelet immunorelated glycoproteins, GPIb, GPIIb IIIa, GPIb IX, and the integrin αv subunit are expressed on the surface of MCF-7 cells. The expression of an immunorelated GPIb was further confirmed by immunoblot and autoradiography of 125I-labelled MCF-7 cells. MCF-7 cell immunoblot preparations demonstrated one major protein reactive to an anti-GPIbα MoAb under nonreduced conditions with a molecular weight of 200 kD and two major proteins reactive with the anti-GPIbα MoAb under reduced conditions with molecular weights of 92 kD and 38 kD. Platelet aggregation is inhibited by preincubating the MCF-7 cells with antibodies to GPIb and GPIIb IIIa. These findings document expression of adhesive glycoproteins by MCF-7 cancer cells and suggest that these receptors, together with ADP, play a role in tumor induced platelet aggregation.
AB - Tumor cell induced platelet aggregation is thought to be an early step in the metastatic process. Here we show that platelet aggregation induced by MCF-7 cells is mediated, in part, through an ADP-dependent mechanism based on inhibition of aggregation by pretreatment of the tumor cells with apyrase and the identification of ADP in tumor cell-free supernatants by HPLC. By applying immunocytochemical and flow cytometric techniques, we demonstrate that platelet immunorelated glycoproteins, GPIb, GPIIb IIIa, GPIb IX, and the integrin αv subunit are expressed on the surface of MCF-7 cells. The expression of an immunorelated GPIb was further confirmed by immunoblot and autoradiography of 125I-labelled MCF-7 cells. MCF-7 cell immunoblot preparations demonstrated one major protein reactive to an anti-GPIbα MoAb under nonreduced conditions with a molecular weight of 200 kD and two major proteins reactive with the anti-GPIbα MoAb under reduced conditions with molecular weights of 92 kD and 38 kD. Platelet aggregation is inhibited by preincubating the MCF-7 cells with antibodies to GPIb and GPIIb IIIa. These findings document expression of adhesive glycoproteins by MCF-7 cancer cells and suggest that these receptors, together with ADP, play a role in tumor induced platelet aggregation.
KW - MCF-7 cultured tumor cells
KW - adenosine diphosphate
KW - breast carcinoma
KW - platelet aggregation
KW - platelet glycoproteins
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U2 - 10.1016/0049-3848(95)00113-6
DO - 10.1016/0049-3848(95)00113-6
M3 - Article
C2 - 8533122
AN - SCOPUS:0029008105
SN - 0049-3848
VL - 79
SP - 261
EP - 274
JO - Thrombosis Research
JF - Thrombosis Research
IS - 3
ER -
