Retaining the long-survive capacity of Circulating Tumor Cells (CTCs) followed by xeno-transplantation: not only from metastatic cancer of the breast but also of prostate cancer patients
Elisabetta Rossi1,2,*, Massimo Rugge3,*, Antonella Facchinetti1,2, Marco Pizzi3, Giorgia Nardo2, Vito Barbieri1, Mariangela Manicone2, Stefania De Faveri2, Maria Chiara Scaini2, Umberto Basso2, Alberto Amadori1,2, Rita Zamarchi2
1 Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova, Padova, Italy
2 IOV-IRCCS, Padova, Italy
3 Department of Medical Diagnostic Sciences & Special Therapies, Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy.
* These authors contributed equally to this work
Correspondence:
Rita Zamarchi, email:
Keywords: Circulating Tumor Cells; EpCAM; prostate cancer; xenograft assay; breast cancer
Received: December 9, 2013 Accepted: December 31, 2013 Published: December 31, 2013
Abstract
We investigated whether Circulating Tumor Cells (CTCs) isolated from epithelial tumors could survive and grow in xenotransplants.
To this purpose, EpCAM-positive CTCs were enriched by CellSearch platform the only FDA-cleared automated platform that quantifies tumor burden in peripheral blood and provides clinical evidence of predictive and prognostic value. The CTCs were isolated from metastatic prostate (n=6) and breast (n=2) cancer patients. The xenograft assay was developed in 8-week-old NOD/SCID mice that were subcutaneously injected with increasing amounts of CTCs (ranging from 50 to 3000).
Human CTCs were found in 8 out of 8 murine peripheral blood (muPB) and in 6 out of 8 murine bone marrow (muBM) samples, after a median follow-up of 10.3 months. Six out of 8 spleens were positive for human cytokeratin. Our assay showed higher successful rate than those previously reported in breast cancer and hepatocellular carcinoma.
The role of EpCAM during carcinogenesis is controversial. The identification of human CTCs in muPB, muBM and spleen demonstrates that the EpCAM-positive fraction of CTCs retains the migratory capacity. This is the first experimental evidence that as few as 50 EpCAM-positive prostate cancer CTCs putatively contain metastasis-initiating-cells (MIC).
