Research Papers:

Tumorigenic potential of circulating prostate tumor cells

Filipe LF. Carvalho _, Brian W. Simons, Emmanuel S. Antonarakis, Zeshaan Rasheed, Nora Douglas, Daniela Villegas, William Matsui and David M. Berman

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Oncotarget. 2012; 4:413-421. https://doi.org/10.18632/oncotarget.895

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Filipe LF. Carvalho1,3, Brian W. Simons1,2, Emmanuel S. Antonarakis3, Zeshaan Rasheed3, Nora Douglas1, Daniela Villegas1, William Matsui3, David M. Berman1,3,4

1 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

2 Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

4 Departments of Pathology and Molecular Medicine and Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada


David M. Berman, email:

Keywords: Circulating tumor cells; EpCAM; prostate cancer; prostate-specific antigen; TRAMP mouse

Received: February 21, 2013 Accepted: March 04, 2013 Published: March 05, 2013


Circulating tumor cells (CTCs) have received intense scientific scrutiny because they travel in the bloodstream and are therefore well situated to mediate hematogenous metastasis. However, the potential of CTCs to actually form new tumors has not been tested. Popular methods of isolating CTCs are biased towards larger, more differentiated, non-viable cells, creating a barrier to testing their tumor forming potential. Without relying on cell size or the expression of differentiation markers, our objective was to isolate viable prostate CTCs from mice and humans and assay their ability to initiate new tumors. Therefore, blood was collected from transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and from human patients with metastatic castration-resistant prostate cancer (PCa). Gradient density centrifugation or red cell lysis was used to remove erythrocytes, and then leukocytes were depleted by magnetic separation using CD45 immunoaffinity beads. CTCs fractions from TRAMP mice and PCa patients were verified by immunocytochemical staining for cytokeratin 8 and EpCAM, and inoculated into immunodeficient mice. TRAMP tumor growth was monitored by palpation. Human tumor growth formation was monitored up to 8 months by ultrasensitive PSA assays performed on mouse serum. We found viable tumor cells present in the bloodstream that were successfully isolated from mice without relying on cell surface markers. Two out of nine immunodeficient mice inoculated with TRAMP CTCs developed massive liver metastases. CTCs were identified in blood from PCa patients but did not form tumors. In conclusion, viable CTCs can be isolated without relying on epithelial surface markers or size fractionation. TRAMP CTCs were tumorigenic, so CTCs isolated in this way contain viable tumor-initiating cells. Only two of nine hosts grew TRAMP tumors and none of the human CTCs formed tumors, which suggests that most CTCs have relatively low tumor-forming potential. Future studies should identify and target the highly tumorigenic cells.

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