BECAS
SOLERNÓ Luisina MarÍa
congresos y reuniones científicas
Título:
IMPACT OF DESMOPRESSIN TREATMENT ON LYMPHOCYTE INFILTRATION AND LUNG PRE-METASTATIC NICHE FORMATION BY COLORECTAL CANCER CELLS
Autor/es:
SOBOL NT; SOLERNÓ LM; LLAVONA C; GOTTARDO MF; SEGATORI V; ALONSO DF; GARONA J
Lugar:
Mar del Plata
Reunión:
Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Metastatic colorectal cancer (mCRC) still stands as a therapeuticchallenge in which tumor cell spread to liver and lungs accounts formost of CRC-related mortality. Desmopressin (dDAVP) is a syntheticvasopressin analog and repurposed hemostatic drug in oncology,with reported antimetastatic and angiostatic action in aggressive tu-mors. Given that the metastatic niche and stroma-tumor cell interac-tions are crucial steps during the establishment of metastases, ouraim was to explore the impact of dDAVP treatment on the pre-meta-static niche formation and the modulation of lymphocyte infiltration inthe lung, the second most common site of metastasis in CRC. First-ly, we characterized the kinetics (7, 15 and 21 days) of lung metas-tases development in syngeneic Balb/c mice after i.v. inoculation ofCT-26 CRC cells, confirming massive tissue colonization and morethan 30 macronodules/lung (>1mm) at day 21. Furthermore, to ass-es the impact of CRC cell-secreted factors on the establishment andgrowth of metastatic cells we injected CT-26 conditioned medium inBalb/c mice prior to tumor cell inoculation for 4 consecutive days,which led to a 3-fold increase in the number of lung metastasis. In-terestingly, this phenomenon was completely reverted after dDAVPco-administration at clinically relevant doses (1 μg/kg i.v.). We thenstudied the impact of dDAVP on the recruitment of inflammatorycells to the lung during the early steps of metastatic colonizationin immunocompetent mice by flow cytometry, where i.v. treatmentwith the peptide significantly increased by 3 times the CD8+ cellpopulation infiltrating the tissue. No significant changes were ob-served in the CD4+ population nor in the circulating CD4+ or CD8+T cells (p
