In Vivo Lymphatic Circulating Tumor Cells and Progression of Metastatic Disease

In Vivo Lymphatic Circulating Tumor Cells and Progression of Metastatic Disease

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 bre...

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Bibliographic Details
Published in:Cancers Vol. 12; no. 10; p. 2866
Main Authors: Han, Mikyung, Watts, Julia Alex, Jamshidi-Parsian, Azemat, Nadeem, Urooba, Sarimollaoglu, Mustafa, Siegel, Eric R., Zharov, Vladimir P., Galanzha, Ekaterina I.
Format: Journal Article
Language:English
Published: Basel MDPI AG 05-10-2020
MDPI
Subjects:
Animal models
Blood
Body fluids
Breast cancer
Cancer cells
Contrast agents
Flow cytometry
Health aspects
Lymph
Lymphatic system
Melanoma
Metastases
Metastasis
Nanoparticles
Statistical analysis
Tumor cells
Tumors
United States
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Summary: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.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12102866