Cell Adhesion Molecules in Colon Cancer Metastasis

Metastasis is a major clinical problem and results in a poor prognosis for most cancers. The metastatic pathway describes the process by which cancer cells give rise to a metastatic lesion in a new tissue or organ. It consists of interconnecting steps all of which must be successfully completed to result in a metastasis. Cell-cell adhesion is a key aspect of many of these steps. Adhesion molecules belonging to the immunoglobulin superfamily (Ig-SF) commonly play a central role in cell-cell adhesion, and a number of these molecules have been associated with cancer progression and a metastatic phenotype. Surprisingly, the contribution of Ig-SF members to metastasis has not received the attention afforded other cell adhesion molecules (CAMs) such as the integrins. Here we examine the steps in the metastatic pathway focusing on how the Ig-SF members, melanoma cell adhesion molecule (MCAM), L1CAM, neural CAM (NCAM), leukocyte CAM (ALCAM), intercellular CAM-1 (ICAM-1) and platelet endothelial CAM-1 (PECAM-1) could play a role. Although much remains to be understood, this review aims to raise the profile of Ig-SF members in metastasis formation and prompt further research that could lead to useful clinical outcomes.

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Role of the interaction between galectin-3 and cell adhesion molecules in cancer metastasis

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2014.11.024 ◽

2015 ◽

Vol 69 ◽

pp. 179-185 ◽

Cited By ~ 26

Author(s):

Ming Xin ◽

Xin-Wen Dong ◽

Xiu-Li Guo

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Cancer Metastasis ◽

Galectin 3

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Heparanase in Cancer Metastasis – Heparin as a Potential Inhibitor of Cell Adhesion Molecules

Advances in Experimental Medicine and Biology - Heparanase ◽

10.1007/978-3-030-34521-1_11 ◽

2020 ◽

pp. 309-329 ◽

Cited By ~ 1

Author(s):

G. Bendas ◽

Lubor Borsig

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Cancer Metastasis ◽

Potential Inhibitor

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Inactivation of E-cadherin by Trop-2 drives colon cancer metastasis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.105 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 105-105

Author(s):

Saverio Alberti ◽

Emanuela Guerra ◽

Donato F. Altomare ◽

Raffaella Depalo ◽

Marco Trerotola

Keyword(s):

Colon Cancer ◽

Cell Adhesion ◽

Cancer Patients ◽

Cancer Metastasis ◽

Colon Cancer Metastasis ◽

Metastatic Relapse ◽

Metastatic Spreading ◽

E Cadherin ◽

Cell Cell

105 Background: Tumor metastasis is the main cause of death of colon cancer patients and the biggest hurdle for cancer cure. We set to identify decisive drivers and of pivotal therapy targets for colon cancer metastasis. Methods: IHC analysis quantified the expression of target molecules in primary tumors and metastases. Cell-cell adhesion capacity was assessed in vitro and in HCT116 colon cancer cell spheroids. Pre-clinical models of orthotopic growth of KM12SM colon cancer cells and metastatic diffusion to the liver were utilized to assess metastatic spreading force of wtTrop-2 and of the constitutively-active, tail-less form of Trop-2 (Δcyto). Xenotransplant and metastasis transcriptomes were analyzed for differential induction of EMT determinants. Kaplan–Meier plots were used to illustrate survival and metastatic relapse in independent case series of colon cancer patients. Results: wtTrop-2 was shown to induce wound-healing. ΔcytoTrop-2 further increased cell migration ability. Both wtTrop-2 and ΔcytoTrop-2 induced resistance to apoptosis in vitro and in vivo. wtTrop-2 strikingly increased the metastatic capacity of KM12SM cells, raising metastasis rates from 45% for control cells to 90% for wtTrop-2 transfectants. The constitutively-active ΔcytoTrop-2 further boosted metastatic spreading, with metastatic livers reaching up to four times their normal size. Cancer metastases revealed high levels of E-cadherin, in the absence of transcriptional down-regulation. EMT transcription factors were largely missing from Trop-2-activated cells. Rather, binding to Trop-2 was shown to cause the release of E-cadherin from the cytoskeleton, loss of cell-cell adhesion and activation of β-catenin. This global, Trop-2/E-cadherin/β-catenin-driven pro-metastatic program was recapitulated in colon cancer patients and was shown to impact on colon cancer metastatic relapse and overall patient survival. Conclusions: We identify Trop-2-driven functional inactivation of E-cadherin as a widespread driver of metastatic diffusion in colon cancer, opening novel avenues for personalized diagnostic procedures and anti-cancer therapies. [Table: see text]

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