In their manuscript “Colorectal cancer cells adhere to traumatized peritoneal tissue in clusters, an experimental study”, Ivarsson and colleagues delineate two interesting models by which the adhesive interaction of colorectal cancer cells with mesothelial cells or peritoneal tissue can be examined in vitro, and demonstrate an increased likelihood of adhesion to traumatized areas in mesothelial monolayers or peritoneal tissue Citation[1]. The issue is an important one. Peritoneal metastasis is common in abdominal cancers such as colorectal or ovarian cancer. It is impossible to distinguish pre-existing peritoneal tumor implantation that was too small to be seen at the time of a putatively curative cancer resection from peritoneal metastasis caused by perioperative tumor dissemination, but we do know that the presence of shed tumor cells at otherwise potentially curative resection is both relatively common and an adverse prognostic sign for colorectal, gastric and gynecologic neoplasms Citation[2-4].
Wound recurrence is a less common specialized example of peritoneal dissemination in which it seems logical to assume that recurrence at the surgical wound most likely reflects perioperative dissemination since the wound was not present prior to surgery. The pivotal multicenter trial that evaluated the safety and efficacy of laparoscopic colorectal cancer resection was underpowered to compare rates of wound recurrence but found a 0.2% incidence of recurrence at the large surgical wounds caused by open resections and a 0.5% incidence of recurrence at the much smaller surgical wounds induced during laparoscopic resection Citation[5]. The incidence of perioperative peritoneal dissemination may be substantially higher.
Perhaps the most important concept here may be the notion that peritoneal dissemination is not just a random accident. It can be investigated, and if it can be understood, it can be inhibited. Our laboratory has investigated the biology of such wound recurrence from the perspective of the tumor cell, tracing an intracellular signal pathway activated by the physical forces present in the surgical environment that upregulates beta1 integrin heterodimer binding affinity for matrix proteins in cancer cells prior to adhesion Citation[6, 7] and a separate pathway in already adherent cells by which increased extracellular pressure stimulates cancer cell proliferation Citation[8, 9]. Blocking such signaling can improve tumor free survival in murine models Citation[10].
The models described here offer the potential for similar studies focusing on the biology of the substrate tissue and its mesothelial cells. Questions about the regulation of the secretion of chemotactic cytokines, expression of cell surface receptors, and synthesis and degradation of matrix proteins by the mesothelial cells in these models can now be asked and answered, and it can be hoped that better understanding of such issues will eventually facilitate the development of interventions targeted at inhibiting peritoneal metastasis.
Declaration of interest: The author reports no conflict of interest. The author alone is responsible for the content and writing of the article.
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