Induction of Premalignant and Malignant Changes in Nude Mice by Human Tumors-Derived Cell-Free Filtrates
Authors:   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, J Berlanga-Acosta , Y Mendoza-Mari ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, I Martinez-Jimenez ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, J Suarez-Alba ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, N Rodriguez-Rodríguez ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, A Garcia-Ojalvo ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, M Fernandez-Mayola ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, P Rosales-Torres ,   Department of Pathology, Maria Curie Oncology Hospital, Carretera Central Oeste esquina Madame Curie, Camagüey, CP, 70 700, Cuba, E Arteaga-Hernandez ,   Department of Pathology, Hermanos Ameijeiras Hospital, Calle San Lazaro # 701, Centro Habana, La Habana 10400, Cuba, D Duvergel-Calderin ,   Department of Pathology, Hermanos Ameijeiras Hospital, Calle San Lazaro # 701, Centro Habana, La Habana 10400, Cuba, I Borrajero-Martinez ,   Department of Pathology, Hermanos Ameijeiras Hospital, Calle San Lazaro # 701, Centro Habana, La Habana 10400, Cuba, A Campal-Espinosa ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, D Fuentes-Morales ,   National Center for Laboratory Animal Breeding, Calle 3ra, No 40759, Entre 6ta y Carretera de Tirabeque, Reparto La Unión, Boyeros, La Habana, Cuba, E Pimentel-Vazquez ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, J Zamora-Sanchez ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba, JE Martinez-Suarez ,   Department of Pathology, Hermanos Ameijeiras Hospital, Calle San Lazaro # 701, Centro Habana, La Habana 10400, Cuba, M Estevez-del Toro ,   Department of Pathology, Hermanos Ameijeiras Hospital, Calle San Lazaro # 701, Centro Habana, La Habana 10400, Cuba, E Gomez-Cabrera ,   National Institute of Oncology and Radiobiology, Calle 29 esquina a F, CP 10 400, Vedado, La Habana, Cuba, G Guillén-Nieto ,   Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Ave 31 SN e/158 and 190, Cubanacan, Playa 10600, Havana, Cuba
Published: January 2023

Carcinogenesis is a vast and heterogeneous, multi-step process driven by genetic and epigenetic operators leading to superimposed “tumor organs”. Based on our previous experiences of reproducing human donor’s histopathological hallmarks in healthy animals exposed to pathologic tissues homogenates, we examined the consequences of administering crude homogenates elaborated from invasive human tumors to nude mice. Subcutaneous administrations of increasing protein concentrations of breast carcinoma homogenates for 6 and 12 weeks, induced lungs atypical adenomatous hyperplasia, foci of lepidic and solid growth poorly-differentiated adenocarcinomas at the two time points. Non-atypical mucosal hyperplasia and adenomas were detected along the gastrointestinal tract. Another experiment addressed the impact of daily administrations (100 μg protein/mouse) of anaplastic sarcoma tissue homogenate for a month. This scheme triggered proliferative changes including: lung adenocarcinomas; a subcutaneous, poorly-differentiated mesenchymal cells tumor, a lymphoadenoma, and multiple gastrointestinal adenomas. When 50% of the month-treated animals were left to evolve treatment-free for other 35 days, a larger and broader incidence of neoplastic changes was found, suggesting autonomous growth: lung adenocarcinomas, a poorly differentiated thyroid tumor, an epithelial tumor within the periaortic brown adipose tissue, and multiple adenomas. These findings indicate that tumor crude homogenates contains soluble “transforming” messengers, that in a short period of time disrupt tissues’ proliferative and differentiation programs drifting to progressive neoplasms. This study expands previous evidences on the ability of human pathologic tissues-derived homogenates, to induce the reproduction of diseased donor’s histopathologic hallmarks.