Berlanga-Acosta Jorge, Arteaga-Hernandez Ernesto, Garcia-Ojalvo Ariana, Duvergel-Calderin Dayanis, Rodriguez-Touseiro Marisol, Lopez-Marin Laura, Suarez-Alba Jose, Fuentes-Morales Dasha, Mendoza-Fuentes Osmany, Fernández-Puentes Sheyla, Nuñez-Figueredo Yanier, Guillen-Nieto Gerardo
Center for Genetic Engineering and Biotechnology, Biomedical Research Direction, Havana, Cuba.
Department of Pathology, Hermanos Ameijeiras Hospital, La Habana, Cuba.
Front Mol Biosci. 2024 Apr 18;11:1361377. doi: 10.3389/fmolb.2024.1361377. eCollection 2024.
Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months. The concurrent control mice received homogenates of healthy donor-skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke the deterioration or mortality of the animals. Multiple foci of lung adenocarcinomas with a broad expression of malignity histomarkers coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers, were detected in lymphoid nodes. The administration of pancreatic tumor and melanoma homogenates progressively deteriorated animal health. Pancreatic tumor induced poorly differentiated lung adenocarcinomas and pancreatic islet hyperplasia. Melanoma affected lungs with solid pseudopapillary adenocarcinomas. Giant atypical hepatocytes were also observed. The kidney exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. Nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in the control mice. Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-M and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for "malignancy drivers," which ultimately implement a carcinogenesis process in otherwise healthy mice.
癌症仍然是全球范围内发病和死亡的原因。研究工作包括向健康动物注射肿瘤提取物。此前已证明，注射不可传播的人类癌症来源的匀浆可在小鼠中诱发恶性肿瘤，在此，我们研究了在两个月内每周进行6次接种，给小鼠注射50或100微克来自乳腺癌、胰腺腺癌和黑色素瘤样本的粗匀浆蛋白的后果。同时，对照小鼠接受健康供体皮肤美容手术碎片的匀浆。注射乳腺癌匀浆并未导致动物健康恶化或死亡。发现了多个肺腺癌病灶，伴有广泛表达的恶性组织标志物，同时存在小细胞样癌。在淋巴结中检测到对经典上皮标志物呈阳性的播散细胞。注射胰腺肿瘤和黑色素瘤匀浆使动物健康状况逐渐恶化。胰腺肿瘤诱发了低分化肺腺癌和胰岛增生。黑色素瘤使肺部出现实性假乳头状腺癌。还观察到巨大的非典型肝细胞。肾脏在纤维增生性基质内出现散在的肿瘤细胞灶。在表皮细胞中发现了核重叠、核深染、有丝分裂象以及明显的核异型性。在对照小鼠中从未检测到这些变化。此外，用乳腺肿瘤匀浆孵育斑马鱼胚胎会诱导c-M和HER-2作为肿瘤标志物的表达，这与暴露于健康组织来源物质的胚胎形成对比。这项研究证实并扩展了我们的假设，即肿瘤匀浆含有并可能作为“恶性驱动因子”的载体，最终在原本健康的小鼠中引发致癌过程。
