MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213)Bi-C595 radioimmunoconjugate.
Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using (213)Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of (213)Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in approximately 90% of tested tumour samples and the three pancreatic cancer cell lines. (213)Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel (213)Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. (213)Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.
Qu
C F
CF
Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St Kogarah, NSW 2217, Australia.
Li
Y
Y
Song
Y J
YJ
Rizvi
S M A
SM
Raja
C
C
Zhang
D
D
Samra
J
J
Smith
R
R
Perkins
A C
AC
Apostolidis
C
C
Allen
B J
BJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D018396:Mucin-1 / Q000096:biosynthesis* / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018796:Immunoconjugates; D018396:Mucin-1