Abstract Number: OC 66.2
Meeting: ISTH 2022 Congress
Background: Tumor metastasis is the principal cause of death in breast cancer patients and the lungs are a disproportionately common site for metastasis. Primary tumors can orchestrate this organotropism by recruiting bone marrow-derived cells (BMDCs) to pre-metastatic lungs, partly through increased lung lysyl oxidase (Lox) expression. In turn, BMDCs create an immune-suppressive microenvironment commonly referred to as the pre-metastatic niche (PMN), which supports the seeding of circulating tumor cells. Although platelets recruit BMDCs during wound healing and promote several hallmarks of metastasis, their contributions to the PMN are unknown.
Aims: The aim of the study was to assess if platelets promote BMDC infiltration into pre-metastatic lungs and to identify platelet cytokines that may recruit BMDCs to the lung PMN.
Methods: Mammary tumors (E0771) were generated in thrombopoietin-deficient (Thpo-/-) mice and lungs extracted for flow cytometric analysis and immunofluorescent staining of cryopreserved tissue sections.
Results: Increased platelet sequestration was observed in the lungs of tumor-bearing Thpo+/+ mice compared to tumor-naïve controls. As expected, platelets were reduced (≈90%) in Thpo-/- mice, with no changes in circulating immune cell populations or primary tumor growth. However, the lungs of Thpo-/- tumor-bearing mice had statistically significant reductions in B cells and inflammatory monocytes, correlating with a reduced Lox staining in lung tissue. Plasma CXCL5 and platelet-derived growth factor were diminished in tumor-bearing Thpo-/- mice and platelets from tumor-bearing mice had increased lipocalin-2, osteopontin, and S100A8/A9, which can be secreted upon platelet activation.
Conclusion(s): The pre-metastatic lungs of platelet-deficient mice had reduced infiltration of metastasis-promoting BMDCs, which could result from reduced Lox expression. Platelets sequestered in pre-metastatic lungs may recruit BMDCs to the PMN by secreting CXCL5, osteopontin, and/or S100A8/9, since they were enriched in several of these niche-promoting factors, suggesting platelet content can be altered by the primary tumor to potentiate the PMN.
To cite this abstract in AMA style:Roweth H, Malloy M, Guo Q, Becker I, McAllister S, Battinelli E. Platelet-mediated potentiation of the lung pre-metastatic niche in breast cancer [abstract]. https://abstracts.isth.org/abstract/platelet-mediated-potentiation-of-the-lung-pre-metastatic-niche-in-breast-cancer/. Accessed September 29, 2023.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-mediated-potentiation-of-the-lung-pre-metastatic-niche-in-breast-cancer/