RESUMO
In recent years, it has become evident that intra-tumor heterogeneity of breast cancer is a big challenge for the diagnosis, treatment, and clinical course of tumor-bearing patients. The advances in molecular biology and other technologies have led to the knowledge that a breast cancer tumor is comprised of multiple cellular entities. Here we review the two theories that have been described, trying to explain the origin of intra-tumor heterogeneity: clonal evolution and cancer stem cells. The first one considers that a single cell gives rise to many subpopulations through the accumulation of multiple aberrations, while the cancer stem cells theory foresees a hierarchical tumor evolution where only a few cells with self-renewal capacity give rise to different subpopulations. We also analyze the genetic, epigenetic, and microenvironment contributions to breast cancer intra-tumor heterogeneity. Finally, the clinical and therapeutic impact of intra-tumor heterogeneity on the outcome of breast cancer patients is discussed.
Assuntos
Neoplasias da Mama/patologia , Evolução Clonal/fisiologia , Células-Tronco Neoplásicas/citologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Autorrenovação Celular/fisiologia , Epigênese Genética/fisiologia , Feminino , Humanos , Biologia Molecular/métodos , Microambiente Tumoral/fisiologiaRESUMO
As regards their morphology and biology, tumours consist of heterogeneous cell populations. The cancer stem cell (CSC) hypothesis assumes that a tumour is hierarchically organized and not all of the cells are equally capable of generating descendants, similarly to normal tissue. The only cells being able to self-renew and produce a heterogeneous tumour cell population are cancer stem cells. CSCs probably derive from normal stem cells, although progenitor cells may be taken into consideration as the source of cancer stem cells. CSCs reside in the niche defined as the microenvironment formed by stromal cells, vasculature and extracellular matrix. The CSC assays include FACS sorting, xenotransplantation to immunodeficient mice (SCID), incubation with Hoechst 33342 dye, cell culture in non-adherent conditions, cell culture with bromodeoxyuridine. CSCs have certain properties that make them resistant to anticancer therapy, which suggests they may be the target for potential therapeutic strategies.
Assuntos
Carcinogênese/patologia , Diferenciação Celular/fisiologia , Autorrenovação Celular/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral/fisiologia , Animais , Biomarcadores Tumorais/uso terapêutico , Evolução Clonal/fisiologia , Matriz Extracelular/patologia , Citometria de Fluxo , Corantes Fluorescentes , Camundongos SCID , Microvasos/fisiopatologia , Prognóstico , Células Estromais/patologiaRESUMO
As regards their morphology and biology, tumours consist of heterogeneous cell populations. The cancer stem cell (CSC) hypothesis assumes that a tumour is hierarchically organized and not all of the cells are equally capable of generating descendants, similarly to normal tissue. The only cells being able to self-renew and produce a heterogeneous tumour cell population are cancer stem cells. CSCs probably derive from normal stem cells, although progenitor cells may be taken into consideration as the source of cancer stem cells. CSCs reside in the niche defined as the microenvironment formed by stromal cells, vasculature and extracellular matrix. The CSC assays include FACS sorting, xenotransplantation to immunodeficient mice (SCID), incubation with Hoechst 33342 dye, cell culture in non-adherent conditions, cell culture with bromodeoxyuridine. CSCs have certain properties that make them resistant to anticancer therapy, which suggests they may be the target for potential therapeutic strategies.