1. In Vivo Lymphatic Circulating Tumor Cells and Progression of Metastatic Disease
- Author
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Julia Watts, Vladimir P. Zharov, Urooba Nadeem, Azemat Jamshidi-Parsian, Mikyung Han, Ekaterina I. Galanzha, Eric R. Siegel, and Mustafa Sarimollaoglu
- Subjects
0301 basic medicine ,Cancer Research ,Sentinel lymph node ,circulating tumor cells ,lcsh:RC254-282 ,Article ,Metastasis ,lymphatic vessels ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Circulating tumor cell ,sentinel lymph node ,medicine ,in vivo flow cytometry ,metastasis ,marker ,business.industry ,Melanoma ,personalized prognosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Primary tumor ,030104 developmental biology ,Lymphatic system ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Lymph ,photoacoustics ,business ,lymphography - Abstract
The dissemination of circulating tumor cells (CTCs) by lymph fluid is one of the key events in the development of tumor metastasis. However, little progress has been made in studying lymphatic CTCs (L-CTCs). Here, we demonstrate the detection of L-CTCs in preclinical mouse models of melanoma and breast cancer using in vivo high-sensitivity photoacoustic and fluorescent flow cytometry. We discovered that L-CTCs are be detected in pre-metastatic disease stage. The smallest primary tumor that shed L-CTCs was measured as 0.094mm×, 0.094mm, its volume was calculated as 0.0004 mm3, and its productivity was estimated as 1 L-CTC per 30 minutes. As the disease progressed, primary tumors continued releasing L-CTCs with certain individual dynamics. The integrated assessment of lymph and blood underlined the parallel dissemination of CTCs at all disease stages. However, the analysis of links between L-CTC counts, blood CTC (B-CTC) counts, primary tumor size and metastasis did not reveal statistically significant correlations, likely due to L-CTC heterogeneity. Altogether, our results showed the feasibility of our diagnostic platform using photoacoustic flow cytometry for preclinical L-CTC research with translational potential. Our findings also demonstrated new insights into lymphatic system involvement in CTC dissemination. They help to lay the scientific foundation for the consideration of L-CTCs as prognostic markers of metastasis and to emphasize the integrative assessment of lymph and blood.
- Published
- 2020
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