Adhesion molecules in peritoneal dissemination: function, prognostic relevance and therapeutic optionsReport as inadecuate

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Clinical and Experimental Metastasis

, Volume 33, Issue 5, pp 401–416

First Online: 13 April 2016Received: 07 December 2015Accepted: 07 April 2016DOI: 10.1007-s10585-016-9791-0

Cite this article as: Sluiter, N., de Cuba, E., Kwakman, R. et al. Clin Exp Metastasis 2016 33: 401. doi:10.1007-s10585-016-9791-0


Peritoneal dissemination is diagnosed in 10–25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2β1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLe and Le, chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLe and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete.

KeywordsPeritoneal metastases Colorectal cancer Hipec Adhesion Predictive biomarkers Prognosis AbbreviationsCRCColorectal carcinoma

PMPeritoneal metastases

PMPPseudomyxoma peritonei

ECMExtracellular matrix

uPAUrokinase plasminogen activator

MDR1Multidrug resistance 1 polypeptide

MRP2Multidrug resistance protein 2

ICAM1Intercellular adhesion molecule

VCAM1Vascular cell adhesion molecule

L1CAML1 cell adhesion molecule

NRP1Neuropilin 1

sLeSialyl Lewis a

LeLewis x

sLeSialyl Lewis x

MUC16Mucin 16

MUC1Mucin 1

EpCAMEpithelial cell adhesion molecule

CXCR4Chemokine C-X-C motif receptor 4

uPARUrokinase receptor

Beta ig-h3Beta induced gene-h3

CX3CL1Chemokine C-X3-C motif ligand 1

IGF-1Insulin-like growth factor 1

HIF-1αHypoxia-inducible factor 1-alpha

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Author: Nina Sluiter - Erienne de Cuba - Riom Kwakman - Geert Kazemier - Gerrit Meijer - Elisabeth Atie te Velde


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