Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors

The leading cause of breast cancer‐associated death is metastasis. In 80% of solid tumors, metastasis via the lymphatic system precedes metastasis via the vascular system. However, the molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sen...

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Main Authors: Sulma I. Mohammed, Odalys Torres‐Luquis, Elwood Walls, Frank Lloyd
Format: Article
Language:English
Published: Wiley 2019-06-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.12494
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author Sulma I. Mohammed
Odalys Torres‐Luquis
Elwood Walls
Frank Lloyd
author_facet Sulma I. Mohammed
Odalys Torres‐Luquis
Elwood Walls
Frank Lloyd
author_sort Sulma I. Mohammed
collection DOAJ
description The leading cause of breast cancer‐associated death is metastasis. In 80% of solid tumors, metastasis via the lymphatic system precedes metastasis via the vascular system. However, the molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. Here, we developed an innovative technique that enables the collection of lymph and lymph‐circulating tumor cells (LCTCs) en route to the SLN in an immunocompetent animal model of breast cancer metastasis. We found that the gene and protein expression profiles of LCTCs and blood‐circulating tumor cells (BCTCs) as they exit the primary tumor are similar, but distinct from those of primary tumors and lymph node metastases (LNMs). LCTCs, but not BCTCs, exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell‐like properties, and are efficient metastatic precursors. These results demonstrate that tumor cells that metastasize through the lymphatic system are different from those spread by blood circulation. Understanding the relative contribution of these cells to overall peripheral blood‐circulating tumor cells is important for cancer therapy. Whether these two types of cell occur in cancer patients remains to be determined.
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spelling doaj.art-503788f71a1a48a5af87328ba9c52c2c2022-12-21T19:18:31ZengWileyMolecular Oncology1574-78911878-02612019-06-011361400141810.1002/1878-0261.12494Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursorsSulma I. Mohammed0Odalys Torres‐Luquis1Elwood Walls2Frank Lloyd3Department of Comparative Pathobiology and Purdue University Center for Cancer Research Purdue University West Lafayette IN USADepartment of Comparative Pathobiology and Purdue University Center for Cancer Research Purdue University West Lafayette IN USADepartment of Basic Medical Sciences Purdue University West Lafayette IN USADepartment of Biomedical Engineering Purdue University West Lafayette IN USAThe leading cause of breast cancer‐associated death is metastasis. In 80% of solid tumors, metastasis via the lymphatic system precedes metastasis via the vascular system. However, the molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. Here, we developed an innovative technique that enables the collection of lymph and lymph‐circulating tumor cells (LCTCs) en route to the SLN in an immunocompetent animal model of breast cancer metastasis. We found that the gene and protein expression profiles of LCTCs and blood‐circulating tumor cells (BCTCs) as they exit the primary tumor are similar, but distinct from those of primary tumors and lymph node metastases (LNMs). LCTCs, but not BCTCs, exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell‐like properties, and are efficient metastatic precursors. These results demonstrate that tumor cells that metastasize through the lymphatic system are different from those spread by blood circulation. Understanding the relative contribution of these cells to overall peripheral blood‐circulating tumor cells is important for cancer therapy. Whether these two types of cell occur in cancer patients remains to be determined.https://doi.org/10.1002/1878-0261.12494breastcancercirculating tumor cellsepithelial‐to‐mesenchymal transitionlymphatic vesselsmetastasis
spellingShingle Sulma I. Mohammed
Odalys Torres‐Luquis
Elwood Walls
Frank Lloyd
Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors
Molecular Oncology
breast
cancer
circulating tumor cells
epithelial‐to‐mesenchymal transition
lymphatic vessels
metastasis
title Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors
title_full Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors
title_fullStr Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors
title_full_unstemmed Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors
title_short Lymph‐circulating tumor cells show distinct properties to blood‐circulating tumor cells and are efficient metastatic precursors
title_sort lymph circulating tumor cells show distinct properties to blood circulating tumor cells and are efficient metastatic precursors
topic breast
cancer
circulating tumor cells
epithelial‐to‐mesenchymal transition
lymphatic vessels
metastasis
url https://doi.org/10.1002/1878-0261.12494
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AT elwoodwalls lymphcirculatingtumorcellsshowdistinctpropertiestobloodcirculatingtumorcellsandareefficientmetastaticprecursors
AT franklloyd lymphcirculatingtumorcellsshowdistinctpropertiestobloodcirculatingtumorcellsandareefficientmetastaticprecursors