The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness
Abstract Circulating tumor cells (CTCs) are important clinical indicators of metastatic progression and treatment efficacy. However, because of their low number and heterogeneity, reliable patient‐derived CTC models are not readily available. We report here the isolation and characterization of the...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-07-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2218 |
| _version_ | 1811270522562936832 |
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| author | Huan Dong Shaun Tulley Qiang Zhao Leong Cho Donghai Chen Michael L. Pearl Wen‐Tien Chen |
| author_facet | Huan Dong Shaun Tulley Qiang Zhao Leong Cho Donghai Chen Michael L. Pearl Wen‐Tien Chen |
| author_sort | Huan Dong |
| collection | DOAJ |
| description | Abstract Circulating tumor cells (CTCs) are important clinical indicators of metastatic progression and treatment efficacy. However, because of their low number and heterogeneity, reliable patient‐derived CTC models are not readily available. We report here the isolation and characterization of the invasive population of CTCs, iCTCs, from blood of 10 patients with epithelial ovarian cancer (EOC) and one pancreatic cancer patient based on the avidity of tumor cells toward an artificial collagen‐based adhesion matrix (CAM), in comparison with tumor progenitor (TP) cells isolated from tumor cell lines, tumors and ascites from EOC patients. CAM‐avid cells identified to be iCTCs were indistinguishable with TP cells using either functional CAM uptake or surface markers (seprase and CD44). In addition, iCTCs were characterized using peritoneal and spontaneous metastasis models in vivo to evaluate their metastatic propensity and therapeutic response. TP cells and iCTCs had a doubling time of about 34‐42 hours. TP cells were rare (<3.5%) in most patient‐derived specimens, however, iCTCs emigrated into blood, at a high frequency, 64.2% (n = 49). Approximately 500 patient‐derived iCTCs recapitulated formation of iCTCs in mouse blood and formed micrometastases in the liver and/or lung, a degree of metastatic spread equivalent to the inoculation of 5 × 105 bulk tumor cells isolated from ascites and tumors. iCTCs were shown to be novel therapeutic targets for blocking metastasis using the reduced formation of iCTCs and micrometastases by RNAi, peptides, and monoclonal antibodies against seprase. |
| first_indexed | 2024-04-12T22:03:27Z |
| format | Article |
| id | doaj.art-f801d1f138a34f379a934870f463d9b0 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-12T22:03:27Z |
| publishDate | 2019-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-f801d1f138a34f379a934870f463d9b02022-12-22T03:15:02ZengWileyCancer Medicine2045-76342019-07-01883864387410.1002/cam4.2218The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsivenessHuan Dong0Shaun Tulley1Qiang Zhao2Leong Cho3Donghai Chen4Michael L. Pearl5Wen‐Tien Chen6Stony Brook Medicine Stony Brook New YorkStony Brook Medicine Stony Brook New YorkStony Brook Medicine Stony Brook New YorkStony Brook Medicine Stony Brook New YorkStony Brook Medicine Stony Brook New YorkStony Brook Medicine Stony Brook New YorkStony Brook Medicine Stony Brook New YorkAbstract Circulating tumor cells (CTCs) are important clinical indicators of metastatic progression and treatment efficacy. However, because of their low number and heterogeneity, reliable patient‐derived CTC models are not readily available. We report here the isolation and characterization of the invasive population of CTCs, iCTCs, from blood of 10 patients with epithelial ovarian cancer (EOC) and one pancreatic cancer patient based on the avidity of tumor cells toward an artificial collagen‐based adhesion matrix (CAM), in comparison with tumor progenitor (TP) cells isolated from tumor cell lines, tumors and ascites from EOC patients. CAM‐avid cells identified to be iCTCs were indistinguishable with TP cells using either functional CAM uptake or surface markers (seprase and CD44). In addition, iCTCs were characterized using peritoneal and spontaneous metastasis models in vivo to evaluate their metastatic propensity and therapeutic response. TP cells and iCTCs had a doubling time of about 34‐42 hours. TP cells were rare (<3.5%) in most patient‐derived specimens, however, iCTCs emigrated into blood, at a high frequency, 64.2% (n = 49). Approximately 500 patient‐derived iCTCs recapitulated formation of iCTCs in mouse blood and formed micrometastases in the liver and/or lung, a degree of metastatic spread equivalent to the inoculation of 5 × 105 bulk tumor cells isolated from ascites and tumors. iCTCs were shown to be novel therapeutic targets for blocking metastasis using the reduced formation of iCTCs and micrometastases by RNAi, peptides, and monoclonal antibodies against seprase.https://doi.org/10.1002/cam4.2218iCTCsmetastasisovarian cancertherapy responsetumor invasion |
| spellingShingle | Huan Dong Shaun Tulley Qiang Zhao Leong Cho Donghai Chen Michael L. Pearl Wen‐Tien Chen The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness Cancer Medicine iCTCs metastasis ovarian cancer therapy response tumor invasion |
| title | The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness |
| title_full | The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness |
| title_fullStr | The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness |
| title_full_unstemmed | The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness |
| title_short | The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness |
| title_sort | propensity of invasive circulating tumor cells ictcs in metastatic progression and therapeutic responsiveness |
| topic | iCTCs metastasis ovarian cancer therapy response tumor invasion |
| url | https://doi.org/10.1002/cam4.2218 |
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