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Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains.

Wang H, Chen NG, Minev BR, Zimmermann M, Aguilar RJ, Zhang Q, Sturm JB, Fend F, Yu YA, Cappello J, Lauer UM, Szalay AA - PLoS ONE (2013)

Bottom Line: Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response.Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer.Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

View Article: PubMed Central - PubMed

Affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.

ABSTRACT
Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

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Related in: MedlinePlus

Characterization of CTCs in blood samples detected with GLV-1h254.(A) The CTCs in mice bearing human PC-3 prostate cancer xenografts showed high-level expression of CD44, ALDH1, vimentin and N-cadherin. (B) The CTCs from the human metastatic breast cancer patient BC1 showed the strong expression of CD44. (C) The live CTCs in the human metastatic breast cancer patient BC5 showed the strong expression of ALDH1.
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pone-0071105-g002: Characterization of CTCs in blood samples detected with GLV-1h254.(A) The CTCs in mice bearing human PC-3 prostate cancer xenografts showed high-level expression of CD44, ALDH1, vimentin and N-cadherin. (B) The CTCs from the human metastatic breast cancer patient BC1 showed the strong expression of CD44. (C) The live CTCs in the human metastatic breast cancer patient BC5 showed the strong expression of ALDH1.

Mentions: Recent studies have indicated that CTCs may be linked to both cancer stem cells (CSCs) and the epithelial-mesenchymal transition (EMT) process [15]–[16]. To elucidate the relationship of CTCs with CSCs and EMT, we analyzed CTCs for the expression of CSC and EMT markers. The CTCs identified with GLV-1h254 in mice bearing human PC-3 prostate cancer xenografts displayed high levels of the expression of the CSC markers CD44 and aldehyde dehydrogenase 1 (ALDH1) as well as the EMT markers vimentin and N-cadherin (Figure 2A). Furthermore, the CTCs identified in the breast cancer patients BC1 and BC5 showed high-level expression of CD44 (Figure 2B) and ALDH1 (Figure 2C), respectively. The features of CSCs as well as phenotypic change characteristics of the EMT possessed by CTCs might allow them to disseminate effectively during the progress of cancer metastases, resulting in the formation of secondary tumors by extravasation and colonization in distant organs.


Optical detection and virotherapy of live metastatic tumor cells in body fluids with vaccinia strains.

Wang H, Chen NG, Minev BR, Zimmermann M, Aguilar RJ, Zhang Q, Sturm JB, Fend F, Yu YA, Cappello J, Lauer UM, Szalay AA - PLoS ONE (2013)

Characterization of CTCs in blood samples detected with GLV-1h254.(A) The CTCs in mice bearing human PC-3 prostate cancer xenografts showed high-level expression of CD44, ALDH1, vimentin and N-cadherin. (B) The CTCs from the human metastatic breast cancer patient BC1 showed the strong expression of CD44. (C) The live CTCs in the human metastatic breast cancer patient BC5 showed the strong expression of ALDH1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760980&req=5

pone-0071105-g002: Characterization of CTCs in blood samples detected with GLV-1h254.(A) The CTCs in mice bearing human PC-3 prostate cancer xenografts showed high-level expression of CD44, ALDH1, vimentin and N-cadherin. (B) The CTCs from the human metastatic breast cancer patient BC1 showed the strong expression of CD44. (C) The live CTCs in the human metastatic breast cancer patient BC5 showed the strong expression of ALDH1.
Mentions: Recent studies have indicated that CTCs may be linked to both cancer stem cells (CSCs) and the epithelial-mesenchymal transition (EMT) process [15]–[16]. To elucidate the relationship of CTCs with CSCs and EMT, we analyzed CTCs for the expression of CSC and EMT markers. The CTCs identified with GLV-1h254 in mice bearing human PC-3 prostate cancer xenografts displayed high levels of the expression of the CSC markers CD44 and aldehyde dehydrogenase 1 (ALDH1) as well as the EMT markers vimentin and N-cadherin (Figure 2A). Furthermore, the CTCs identified in the breast cancer patients BC1 and BC5 showed high-level expression of CD44 (Figure 2B) and ALDH1 (Figure 2C), respectively. The features of CSCs as well as phenotypic change characteristics of the EMT possessed by CTCs might allow them to disseminate effectively during the progress of cancer metastases, resulting in the formation of secondary tumors by extravasation and colonization in distant organs.

Bottom Line: Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response.Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer.Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

View Article: PubMed Central - PubMed

Affiliation: Genelux Corporation, San Diego Science Center, San Diego, California, United States of America.

ABSTRACT
Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

Show MeSH
Related in: MedlinePlus