The non-vesicle cell-free DNA (cfDNA) induces cell transformation associated with horizontal DNA transfer.

BACKGROUND: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins. The present study aimed to demonstrate whether cfDNA not associated with EV induces cell transformation and tumorigenesis. METHODS: Supernatant of the SW480 human colon cancer cell line was processed by ultracentrifugation to obtain a soluble fraction (SF) and a fraction associated with EV (EVF). Primary murine embryonic fibroblast cells (NIH3T3) underwent passive transfection with these fractions, and cell proliferation, cell cycle, apoptosis, cell transformation, and tumorigenic assays were performed. Next, cfDNA was analyzed by electronic microscopy, and horizontal transfer was assessed by human mutant KRAS in recipient cells via PCR and recipient cell internalization via fluorescence microscopy. RESULTS: The results showed that the SF but not the EVF of cfDNA induced proliferative and antiapoptotic effects, cell transformation, and tumorigenesis in nude mice, which were reduced by digestion with DNAse I and proteinase K. These effects were associated with horizontal DNA transfer and cfDNA internalization into recipient cells. CONCLUSIONS: The results suggest pro-tumorigenic effects of cfDNA in the SF that can be offset by enzyme treatment. Further exploration of the horizontal tumor progression phenomenon mediated by cfDNA is needed to determine whether its manipulation may play a role in cancer therapy.

Bases moleculares de la carcinogénesis viral de papiloma y polioma / The molecular bases of papilomavirus and polyomavirus carcinogenesis

El virus de polioma es capaz de inducir tumores en sus hospederos naturales y transformar células en cultivo. Por otro lado, el virus de papiloma humano se ha relacionado con diversos tipos de neoplasias; de manera particular con lesiones anogenitales humanas. No se conoce con exactitud el mecanismo a través del cual estos virus inducen transformación y tumorigénesis. El presente trabajo muestra algunas de las características de los mecanismos que utilizan los virus mencionados para participar en la transformación y tumorigénesis. Además, se ha encontrado que ciertos aspectos de la infección por el virus de polioma son parecidos a la infección del virus del papiloma (ambos pertenecen a la misma familia Papovaviridae), por lo que se consideran algunas semejanzas y diferencias entre los mismos

Polyomavirus is able to induce tumors in its natural host as well as to transform cells in cultures. On the other hand, human papillomavirus has been involved in several types of neoplasias such as anogenital lesions. Little is known about the mechanisms through which these viruses induce both transformation and tumorigenesis. The present work shows some characteristics of the mechanisms that papillomavirus and polyomavirus use to participate in tumorigenesis. It has also been noticed that the infection caused by polyomavirus resembles that performed by papillomaviruses (which belong to the same Papovaviridae family). Some similarities and differences between these viruses are considered.