New experimental markers for early detection of high-risk prostate cancer: role of cell–cell adhesion and cell migration

Today’s treatment and diagnosis of prostate cancer still exhibit major limitations. The search for new and additional prognostic markers is therefore still an actual field of interest. Potential markers involved in numerous biological processes in the tumor cell have been investigated intensively. For therapeutic interventions it is important to distinguish between harmless and aggressive disease in an early stage. Therefore the subject of this review is limited to markers associated with those functional processes, which discriminate early stage aggressive, metastatic cancer from harmless disease. Important processes in this respect are: altered cell adhesion and cellular migration. E-cadherin, N-cadherin, β-catenin, integrins, focal adhesion kinase, connexins and matrix metalloproteinases all appear promising biological markers associated with the early stage metastatic process in prostate cancer. Here we discuss their potential to become valid biological markers based on literature data. Thus far, none of these markers proved to be a valid individual marker by itself due to prostate cancer heterogeneity and transient expression. Analyzing a combination of the potential markers discussed in this review is expected to be a better approach toward discriminating high- from low-risk tumors in an early stage of prostate cancer.

[1]  K. Pienta,et al.  E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology. , 2001, Human pathology.

[2]  W. Isaacs,et al.  In vitro evidence for complex modes of nuclear β-catenin signaling during prostate growth and tumorigenesis , 2002, Oncogene.

[3]  D. Johnston,et al.  The relative mRNA expression levels of matrix metalloproteinase to E-cadherin in prostate biopsy specimens distinguishes organ-confined from advanced prostate cancer at radical prostatectomy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[4]  M. Mesnil.  Connexins and cancer , 2002, Biology of the cell.

[5]  R. Kittles,et al.  E‐cadherin polymorphisms and haplotypes influence risk for prostate cancer , 2006, The Prostate.

[6]  S. Brewster,et al.  Wnt signalling and prostate cancer , 2005, Prostate Cancer and Prostatic Diseases.

[7]  B. Knudsen,et al.  The impact of cell adhesion changes on proliferation and survival during prostate cancer development and progression , 2006, Journal of cellular biochemistry.

[8]  H. Beug,et al.  Molecular requirements for epithelial-mesenchymal transition during tumor progression. , 2005, Current opinion in cell biology.

[9]  L. Klotz.  Active surveillance with selective delayed intervention for favorable risk prostate cancer. , 2006, Urologic oncology.

[10]  L. Kiemeney,et al.  Single‐nucleotide polymorphism in the E‐cadherin gene promoter modifies the risk of prostate cancer , 2002 .

[11]  R. Nagle,et al.  Unique expression pattern of the α6β4 integrin and laminin‐5 in human prostate carcinoma , 2001 .

[12]  L. Bégin,et al.  Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma , 1996, International journal of cancer.

[13]  R. Nagle,et al.  The α6β1 and α6β4 integrins in human prostate cancer progression , 1995, Cancer and Metastasis Reviews.

[14]  J. Kench,et al.  Lower levels of nuclear β‐catenin predict for a poorer prognosis in localized prostate cancer , 2005, International journal of cancer.

[15]  R. Nagle,et al.  The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression. , 1995, Cancer metastasis reviews.

[16]  Xi Lin,et al.  Changes in gap junctional connexin isoforms during prostate cancer progression , 2006, The Prostate.

[17]  J. Mohler,et al.  In situ hybridization studies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2 expression in human prostate cancer , 1997, Clinical & Experimental Metastasis.

[18]  E. Crawford,et al.  Epidemiology of prostate cancer. , 2003, Urology.

[19]  J. Downward.  PI 3-kinase, Akt and cell survival. , 2004, Seminars in cell & developmental biology.

[20]  Lynette M. Smith,et al.  Aberrant expression of E-cadherin and beta-catenin in human prostate cancer. , 2005, Urologic oncology.

[21]  H. Grönberg,et al.  −160C/A polymorphism in the E‐cadherin gene promoter and risk of hereditary, familial and sporadic prostate cancer , 2004, International journal of cancer.

[22]  G. Morgia,et al.  Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer , 2005, Urological Research.

[23]  Erik Sahai,et al.  Mechanisms of cancer cell invasion. , 2005, Current opinion in genetics & development.

[24]  Arul M Chinnaiyan,et al.  Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer. , 2003, Journal of the National Cancer Institute.

[25]  A. Lu,et al.  Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml. correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml. , 2002, The Journal of urology.

[26]  W. Zheng,et al.  E-cadherin promoter polymorphisms are not associated with the aggressiveness of prostate cancer in Caucasian patients. , 2006, Urologic oncology.

[27]  Lynette M. Smith,et al.  N‐cadherin switching occurs in high Gleason grade prostate cancer , 2006, The Prostate.

[28]  H. Habermann,et al.  Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer. , 2001, The Journal of urology.

[29]  J. Thiery.  Epithelial–mesenchymal transitions in tumour progression , 2002, Nature Reviews Cancer.

[30]  B. Boyer,et al.  Induction and regulation of epithelial-mesenchymal transitions. , 2000, Biochemical pharmacology.

[31]  H. Beug,et al.  Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis , 2003, Nature Reviews Molecular Cell Biology.

[32]  Dominique Trudel,et al.  An immunohistochemical study , 2013 .

[33]  Robert A Sikes,et al.  Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer , 2004, Reproductive biology and endocrinology : RB&E.

[34]  R. Nagle,et al.  Unique expression pattern of the alpha6beta4 integrin and laminin-5 in human prostate carcinoma. , 2001, The Prostate.

[35]  H. Frierson,et al.  Expression of focal adhesion kinase in normal and pathologic human prostate tissues , 2002, The Prostate.