ABSTRACT
The tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cells, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs is crucial for enhancing treatment outcome and reducing the burden of toxicity. In this review, we have provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we dissected the signaling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and further suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.
ABSTRACT
Infectious origins of a set of severe gastroduodenal diseases viz. gastritis, duodenal ulcer, gastric ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma were appreciated only after the discovery of H. pylori in 1983. In the past two decades, however, findings from many laboratories suggest that apart from H. pylori, several of the trillions of microbes that populate the human gastrointestinal tract and form microbiomes of the respective niches (like oral microbiome, esophageal microbiome, gastric microbiome and intestinal microbiome) may also participate in maintaining the healthy state of stomach and duodenum. Dysbiosis leading to alteration in the relative abundance of the key gastrointestinal microbes is associated with severe gastric diseases. For instance, an increased abundance of genera like Leptotrichia, Prevotella and Veillonella in gastric microbiome and a decreased abundance of Bifidobacterium in intestinal microbiome are associated with gastric cancer. H. pylori infection, apart from causing direct harm to the gastric epithelium by its virulence proteins like vacuolating cytotoxin A (VacA) and cytotoxin associated gene A (CagA), is also capable of triggering dysbiosis in stomach and intestinal microbiomes. In this chapter, we have discussed the possible roles of bacteria, viruses, fungi, archaea, protozoa and helminths in human gastrointestinal tracts in the context of H. pylori infection in stomach and various gastroduodenal diseases.
Subject(s)
Gastrointestinal Microbiome , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/genetics , Dysbiosis/complications , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Stomach , Stomach Neoplasms/microbiology , CytotoxinsABSTRACT
It is increasingly being recognized that severe gastroduodenal diseases such as peptic ulcer and gastric cancer are not just the outcomes of Helicobacter pylori infection in the stomach. Rather, both diseases develop and progress due to the perfect storms created by a combination of multiple factors such as the expression of different H. pylori virulence proteins, consequent human immune responses, and dysbiosis in gastrointestinal microbiomes. In this mini review, we have discussed how the genomes of H. pylori and other gastrointestinal microbes as well as the genomes of different human populations encode complex and variable virulome-immunome interplay, which influences gastroduodenal health. The heterogeneities that are encrypted in the genomes of different human populations and in the genomes of their respective resident microbes partly explain the inconsistencies in clinical outcomes among the H. pylori-infected people.