Yayoi Adachi1,2, Mayumi Yoshimura3, Keiko Nishida3, Hisanobu Usuki4, Keiko Shibata4, Masaya Hattori2, Naoto Kondo2, Yasushi Yatabe3, Hiroji Iwata2, Toyone Kikumori1, Yasuhiro Kodera5, Hayao Nakanishi6,7. 1. Department of Transplantation and Endocrine Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8560, Japan. 2. Department of Breast Oncology, Aichi Cancer Center Central Hospital, 1-1 Kanokoden, Chikusa, Nagoya, 464-8681, Japan. 3. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, 1-1, Kanokoden, Chikusa, Nagoya, 464-8681, Japan. 4. Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, 18 Kuriyada Kakemachi, Okazaki, 444-0011, Japan. 5. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8560, Japan. 6. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, 1-1, Kanokoden, Chikusa, Nagoya, 464-8681, Japan. hnakanis@aichi-cc.jp. 7. Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, 18 Kuriyada Kakemachi, Okazaki, 444-0011, Japan. hnakanis@aichi-cc.jp.
Abstract
PURPOSE: Circulating tumor cells (CTCs) can provide a potentially minimal invasive source for monitoring chemotherapeutic effects. However, detailed in vivo dynamics of CTC after chemotherapy remain largely unknown. METHODS: We monitored CTC number and morphology early after chemotherapy using a newly developed cytology-based CTC detection device and triple-negative breast cancer mouse CTC models with spontaneous lung metastatic potential. RESULTS: Paclitaxel inhibited cell growth of breast cancer cells by mainly G2/M cell cycle arrest and partly apoptosis, whereas doxorubicin inhibited cell growth mainly by apoptosis and partly G2 cell cycle arrest in vitro. The number of CTCs was significantly increased 3-10 days after paclitaxel and doxorubicin chemotherapy and decreased thereafter in two mouse CTC models. The transiently increased CTCs early post-chemotherapy consisted of not only G2/M arrested cells (apoptotic cells), but also morphologically near-intact live cells. This heterogeneous cell population of CTCs was similar to that of primary tumor tissue after chemotherapy. CONCLUSIONS: These results indicate that CTCs can be mobilized from the primary tumor in rapid response to chemotherapy and suggest the possibility that CTC monitoring from both numerical and morphological viewpoints early after chemotherapy using a cytology-based CTC detection device would be a useful diagnostic tool for predicting drug sensitivity/resistance in preclinical and clinical setting.
PURPOSE: Circulating tumor cells (CTCs) can provide a potentially minimal invasive source for monitoring chemotherapeutic effects. However, detailed in vivo dynamics of CTC after chemotherapy remain largely unknown. METHODS: We monitored CTC number and morphology early after chemotherapy using a newly developed cytology-based CTC detection device and triple-negative breast cancermouse CTC models with spontaneous lung metastatic potential. RESULTS:Paclitaxel inhibited cell growth of breast cancer cells by mainly G2/M cell cycle arrest and partly apoptosis, whereas doxorubicin inhibited cell growth mainly by apoptosis and partly G2 cell cycle arrest in vitro. The number of CTCs was significantly increased 3-10 days after paclitaxel and doxorubicin chemotherapy and decreased thereafter in two mouse CTC models. The transiently increased CTCs early post-chemotherapy consisted of not only G2/M arrested cells (apoptotic cells), but also morphologically near-intact live cells. This heterogeneous cell population of CTCs was similar to that of primary tumor tissue after chemotherapy. CONCLUSIONS: These results indicate that CTCs can be mobilized from the primary tumor in rapid response to chemotherapy and suggest the possibility that CTC monitoring from both numerical and morphological viewpoints early after chemotherapy using a cytology-based CTC detection device would be a useful diagnostic tool for predicting drug sensitivity/resistance in preclinical and clinical setting.
Entities:
Keywords:
Breast cancer; CTC; Chemotherapy; Cytology; In vivo dynamics; Preclinical study