Catálogo de publicaciones - revistas

<jats:p>Tumor cells may send out tiny vesicles that prime organs for cancer to spread</jats:p>

<jats:p>Despite decades of study, there are still many unanswered questions about metastasis, the process by which a localized cancer becomes a systemic disease. One of these questions is the nature of the tumor cells that give rise to metastases. Although conventional models suggest that metastases are seeded by single cells from the primary tumor, there is growing evidence that seeding requires the collective action of tumor cells traveling together in clusters. Here, we review this evidence, which comes from analysis of both experimental models and patient samples. We present a model of metastatic dissemination that highlights the activities of clusters of tumor cells that retain and require their epithelial properties.</jats:p>

<jats:p>Therapeutic advances in oncology have not fully translated to the treatment of metastatic disease, which remains largely incurable. Metastatic subclones can emerge both early and late in the life of the primary tumor. A better understanding of the genetic evolution of metastatic disease has the potential to reveal differences in the therapeutic vulnerabilities of primary and metastatic tumors, shed light on the temporal patterns of and routes to metastatic colonization, and provide insight into the biology of the metastatic process. Here we review recent comparative studies of primary and metastatic tumors, including data suggesting that macroevolutionary shifts (the onset of chromosomal instability) contribute to the evolution of metastatic disease. We also discuss the practical challenges associated with these studies and how they might be overcome.</jats:p>

<jats:p>Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Hypoxia is a potent microenvironmental factor promoting metastatic progression. Clinically, hypoxia and the expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 are associated with increased distant metastasis and poor survival in a variety of tumor types. Moreover, HIF signaling in malignant cells influences multiple steps within the metastatic cascade. Here we review research focused on elucidating the mechanisms by which the hypoxic tumor microenvironment promotes metastatic progression. These studies have identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at preventing and treating metastatic disease.</jats:p>