Molecular mechanisms of peritoneal dissemination in gastric cancer

Abstract

Peritoneal dissemination represents a devastating form of gastric cancer (GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

“…In metastatic gastric cancer, direct seeding into the peritoneal cavity occurs in more than 50% of patients (3). The development of peritoneal dissemination occurs when gastric cancer cells exfoliate from the serosa of the stomach into the abdominal cavity, where they survive before attaching to peritoneal mesothelial cells and invading into the basement membrane to finally induce angiogenesis (3). Exosomes have been revealed to be important mediators of this process, as summarized in Fig.…”

“…Epithelial cells express high levels of epithelial (E)-cadherin, while mesenchymal cells express neural (N)-cadherin, fibronectin and vimentin (14). Dysfunction of E-cadherin has been implicated in gastric cancer progression and may predominantly contribute to invasion of the gastric wall and migration of cancer cells into the free abdominal space (3). Exosomes may induce epithelial-to-mesenchymal transition (EMT), triggering the loss of cell-cell adhesion to facilitate tumor cell invasion and remodeling of the extracellular matrix.…”

“…Gastric cancer patients with peritoneal dissemination cannot undergo radical surgery, and the chemotherapeutic effect is limited due to inadequate distribution of intravenous chemotherapy drugs, blocked by the peritoneal barrier, and tumor chemoresistance (2). The 5-year survival rate of gastric cancer patients with peritoneal dissemination is only 2% (3). Peritoneal dissemination is among the most common patterns of recurrence in gastric cancer patients (4).…”

Exosomes: The New Mediator of Peritoneal Membrane Function

“…Similarly, metastatic tumor cells express matrix proteinases that disrupt the peritoneal blood barrier and attachment to the PM, enabling invasion into the subperitoneal space and proliferation in response to angiogenesis. Subsequently, angiogenesis is crucial for progressive PM lesions [42].…”

Molecular mechanism of peritoneal dissemination in gastric cancer

“…However, the mesothelium, a membrane composed of simple squamous epithelium that forms the lining of peritoneum, prevents the cancer cells from penetrating into the submesothelial space. The connective tissue under the mesothelium contributes to the formation of a microenvironment (niche) for seeding cancer nodules in the process of PD [6,57,58] . The production of MMPs and integrin is important for the penetration into the submesothelial space [59] .…”