Use of guanylyl cyclase c for detecting micrometastases in lymph nodes of patients with colon cancer

Abstract

Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers might be useful to more accurately assess micrometastases in lymph nodes of colorectal cancer patients undergoing disease staging.

Guanylyl cyclase C agonists regulate progression through the cell cycle of human colon carcinoma cells

“…In intestine, GC-C is expressed along a crypt-to-villus gradient, with the greatest expression in the mid-villus where enterocytes transition from proliferation to differentiation, suggesting that GC-C may play a role in regulating that transition (22,23). Also, expression of GC-C is highly conserved, whereas that of guanylin is significantly reduced, in proliferating colorectal cancer cells and tumors (10,(24)(25)(26)(27). In addition, oral uroguanylin reduced the formation of polyps in the Min͞ϩ mouse model of colon cancer (27).…”

Emergent Concepts from the Intestinal Guanylyl Cyclase C Pathway

“…In that context, since its inception primary colorectal cancer consists of biologically heterogeneous cell subpopulations, among which are present those possessing the ability to migrate and spread to distant parenchyma (Fidler, 2003;Heppner, 1984). Intriguingly as demonstrated by extensive immune detection and mRNA analyses of clinical specimens, GCC is uniformly expressed in metastatic colon tumors regardless of anatomical location (Carrithers et al, 1994;Carrithers et al, 1996;Waldman et al, 1998). Moreover, the structural and functional integrity of GCC and its principal downstream effectors appears to be preserved in metastasis, as colorectal cancer cells at extra-intestinal sites exhibit identical binding characteristics to, and signalling activation by, the exogenous ligand ST to those of normal intestinal cells (Carrithers et al, 1994;Schulz et al, 2006;Witek et al, 2005).…”

“…Thus, detection of hormone downregulation in colon biopsies could indicate presence of intestinal carcinogenesis and demand appropriate follow-up (Cohen et al, 1998;Notterman et al, 2001). The selective expression of GCC in colorectal tumor cells at metastatic sites (Carrithers et al, 1994(Carrithers et al, , 1996Waldman et al, 1998), suggests its utility as a diagnostic marker and specific target for delivering imaging and therapeutic agents in vivo (Gali et al, 2001;Wolfe et al, 2002). Indeed, clinical trials are confirming the value of GCC as a diagnostic marker for molecular staging of patients and prognostic indicator of colorectal cancer recurrence (Mejia et al, 2010;Waldman et al, 2009).…”

Molecular Testing for Lymph Node Metastases as a Determinant of Colon Cancer Recurrence: Results from a Retrospective Multicenter Study

“…One way to overcome standard practice limitations is to increase sampling of the specimen and to identify clinically relevant lymph node metastases that may not have been observed by manual microscopic examination. As such, molecular detection of guanylyl cyclase C (GCC) may be a particularly sensitive and specific method for the detection of colorectal tumor cells in extraintestinal tissues and could identify pN0 colon cancer patients at increased recurrence risk (8)(9)(10). GCC is a human receptor for the gastrointestinal hormones, guanylin and uroguanylin, normally found in the luminal aspect of intestinal epithelium and whose expression is preserved in primary and metastatic colorectal cancer cells (11).…”