Cancer as an Embryological Phenomenon and Its Developmental Pathways: A Hypothesis regarding the Contribution of the Noncanonical Wnt Pathway.

For gastrulation to occur in human embryos, a mechanism that simultaneously regulates many different processes, such as cell differentiation, proliferation, migration, and invasion, is required to consistently and effectively create a human being during embryonic morphogenesis. The striking similarities in the processes of cancer and gastrulation have prompted speculation regarding the developmental pathways involved in their regulation. One of the fundamental requirements for the developmental pathways in gastrulation and cancer is the ability to respond to environmental stimuli, and it has been proposed that the Kaiso and noncanonical Wnt pathways participate in the mechanisms regulating these developmental pathways. In particular, these pathways might also explain the notable differences in invasive capacity between cancers of endodermal and mesodermal origins and cancers of ectodermal origin. Nevertheless, the available information indicates that cancer is an abnormal state of adult human cells in which developmental pathways are reactivated in inappropriate temporal and spatial contexts.

The first embryo, the origin of cancer and animal phylogeny. I. A presentation of the neoplastic process and its connection with cell fusion and germline formation.

The decisive role of Embryology in understanding the evolution of animal forms is founded and deeply rooted in the history of science. It is recognized that the emergence of multicellularity would not have been possible without the formation of the first embryo. We speculate that biophysical phenomena and the surrounding environment of the Ediacaran ocean were instrumental in co-opting a neoplastic functional module (NFM) within the nucleus of the first zygote. Thus, the neoplastic process, understood here as a biological phenomenon with profound embryologic implications, served as the evolutionary engine that favored the formation of the first embryo and cancerous diseases and allowed to coherently create and recreate body shapes in different animal groups during evolution. In this article, we provide a deep reflection on the Physics of the first embryogenesis and its contribution to the exaptation of additional NFM components, such as the extracellular matrix. Knowledge of NFM components, structure, dynamics, and origin advances our understanding of the numerous possibilities and different innovations that embryos have undergone to create animal forms via Neoplasia during evolutionary radiation. The developmental pathways of Neoplasia have their origins in ctenophores and were consolidated in mammals and other apical groups.

Sepsis affects cardiac expression of multidrug resistance protein 5 (MRP5, ABCC5), an ABC-type CGMP export pump.

One of the clinical characteristics associated with septic shock is heart failure. Several lines of evidence indicate that functional consequences of heart failure in septic shock are linked to the activated NO-cyclic guanosine monophosphate (NO-cGMP) pathway. We have previously shown that the high-affinity cGMP export transporter, multidrug resistance protein 5 (MRP5), is expressed in the heart, which modulates intracellular concentrations and, hence, the effects of cGMP. Thus, modified expression of cardiac MRP5 in septic shock can alter cGMP concentrations and contribute to the development of heart failure. We therefore investigated MRP5 expression in the heart using two established murine models of septic shock (intraperitoneal LPS injection and surgical implantation of a stent into the ascending colon, resulting in a multibacterial peritonitis [CASP, colon ascendens stent peritonitis] in C57BL/6N mice, respectively; n = 38). Cardiac MRP5 was assessed by quantitative polymerase chain reaction and immunofluorescence. The protein was localized in the endothelial wall, smooth muscle, and cardiac myocytes. MRP5 mRNA expression was significantly reduced compared with controls both in the LPS (31.9 +/- 16.8 x 10(-4) vs. 54.1 +/- 14.8 x 10(-4), P = 0.025) and CASP model (18.3 +/- 9.4 x 10(-4) vs. 42.8 +/- 12.1 x 10(-4), P = 0.009; MRP5/glyceraldehyde 3-phosphate dehydrogenase copy numbers, respectively). In parallel, IL-6 plasma levels were significantly increased in both models. Incubation of cultured murine cardiomyocytes (HL1) with 5 ng/mL IL-6 resulted in decreased expression of MRP5 (54% of control), as did incubation of the cells with serum from septic mice (LPS serum, 22% of control; CASP serum, 11% of control). In conclusion, cardiac expression of the cGMP export transporter MRP5 is decreased in two murine models of septic shock, most likely by a transcriptional mechanism. Reduced cGMP export as a consequence of decreased MRP5 expression can attenuate heart failure in sepsis.