Expression profile of standard and variants forms of CD44 related to prostate cancer behavior (original) (raw)
Related papers
Decreased expression of cd44 in metastatic prostate cancer
International Journal of Cancer, 1999
Decreased expression of CD44 is an independent prognostic marker for surgically treated prostate cancer. To investigate immunohistochemically defined CD44 expression in primary and metastatic prostate cancer, 2 groups of patients undergoing radical prostatectomy for clinically localized prostate cancer were studied. (1) pN 1 group: 23 patients, finally staged pN 1 , of whom the radical prostatectomy specimen and the lymph nodes were investigated to establish a correlation between CD44 expression in the concurrently resected primaries and metastases; (2) pN 0 group: 23 patients with pN 0 disease matched for pT stage and Gleason sum score with the pN 1 patients. Progression rates based on serum prostatespecific antigen (PSA) levels could be determined in 42 of these 46 patients. In addition, 28 distant metastases were studied. A CD44 score of F 10% was found in 22 of the 23 lymph node metastases (96%) and in 20 of the corresponding radical prostatectomies. In the pN 0 group this was observed in only 6 out of 23 specimens. In most of the distant metastases CD44 scores were F 10%. Patients with pN 0 disease and G 10% CD44-positive tumor cells had a significantly better prognosis than the other patients who were not significantly different from each other. CD44 expression is thus strongly reduced in prostate cancer metastases as well as in the corresponding primary tumors. This reduction may be used to predict the N stage clinically, provided that CD44 scores can be determined reliably on preoperative biopsy specimens.
DECREASED CD44 EXPRESSION IN METASTATIC PROSTATE CANCER
J Urol, 1999
Decreased expression of CD44 is an independent prognostic marker for surgically treated prostate cancer. To investigate immunohistochemically defined CD44 expression in primary and metastatic prostate cancer, 2 groups of patients undergoing radical prostatectomy for clinically localized prostate cancer were studied. (1) pN 1 group: 23 patients, finally staged pN 1 , of whom the radical prostatectomy specimen and the lymph nodes were investigated to establish a correlation between CD44 expression in the concurrently resected primaries and metastases; (2) pN 0 group: 23 patients with pN 0 disease matched for pT stage and Gleason sum score with the pN 1 patients. Progression rates based on serum prostatespecific antigen (PSA) levels could be determined in 42 of these 46 patients. In addition, 28 distant metastases were studied. A CD44 score of F 10% was found in 22 of the 23 lymph node metastases (96%) and in 20 of the corresponding radical prostatectomies. In the pN 0 group this was observed in only 6 out of 23 specimens. In most of the distant metastases CD44 scores were F 10%. Patients with pN 0 disease and G 10% CD44-positive tumor cells had a significantly better prognosis than the other patients who were not significantly different from each other. CD44 expression is thus strongly reduced in prostate cancer metastases as well as in the corresponding primary tumors. This reduction may be used to predict the N stage clinically, provided that CD44 scores can be determined reliably on preoperative biopsy specimens.
Silencing of CD44 Expression in Prostate Cancer by Hypermethylation of the CD44 Promoter Region
Laboratory Investigation, 2000
Loss of the CD44 transmembrane glycoprotein in primary prostate cancer has been shown to be associated with unfavorable clinical behavior. Moreover, the majority of prostate cancer metastases lack expression of this molecule. The mechanism of CD44 silencing in prostate cancer was investigated using both patient material and in vivo-propagated human prostate cancer xenografts. In 9 of 11 lymph node metastases of prostate cancer, we demonstrated by methylation-sensitive restriction enzyme digestion that the promoter region of the CD44 gene is methylated, indicating that this represents a major mechanism of CD44 silencing. Similarly, in 6 out of 12 in vivo-growing human prostate carcinoma xenograft models, hypermethylation of the CD44 gene was found. The extent of CpG island methylation was investigated by nucleotide sequencing after bisulphite modification of the CD44 promoter region. In the xenografts displaying hypermethylation, the examined 14 CpG sites in the CD44 transcription regulatory domain, including a Sp1 binding site, were consistently methylated. This correlated with reduced CD44 expression or lack of CD44 expression at mRNA and protein levels. In the xenografts lacking hypermethylation of the CD44 gene, high levels of CD44 mRNA and protein were expressed in some models, whereas in others CD44 mRNA expression was only detectable by RT-PCR and the CD44 protein could hardly be detected or was not detected at all. The results indicate that, in most prostate cancers, loss of CD44 expression is associated with extensive hypermethylation of the CpG island of the CD44 promoter region, but other, posttranscriptional mechanisms may also lead
The CD44 Isoforms in Prostate Cancer Metastasis and Progression
World Journal of Cancer Research
Prostate cancer (CaP) is a major health problem in males in Western countries. Current therapeutic approaches are limited, especially for castration-resistant CaP or secondary disease. CD44, being designated a cancer stem cell (CSC) marker, is widely involved in cell adhesion, migration and drug resistance in CaP. However divergent functions have been attributed to a variety of CD44 isoforms. Although CD44 has been broadly investigated in cancers by many research groups, understanding the roles of each CD44 isoform in cancer research is still in its infancy. As CD44 could be an ideal therapeutic target for the control of late stage metastatic CaP, it will be particularly interesting and important to study the specific roles of each isoform or combination of isoforms, and how they are regulated. In this review, we summarize the expression of CD44 isoforms in CaP tissues and cell lines from our recent observation and discuss the potential mechanisms controlling their transformation. We also investigate the potential roles of CD44 isoforms as CSC markers in CaP metastasis. Finally, emerging and innovative approaches to the management of cancers with CD44 conjugates and expanding potential therapeutic applications of CD44 isoforms for targeted strategies in future CaP therapy will be explored.
The Journal of urology, 2002
A third of the patients treated with radical prostatectomy experience progression even when tumors are confined pathologically to the prostate. CD44 may be a promising prognostic marker for determining malignant potential. However, there has not been a standard scoring system because of its heterogeneous staining pattern. Thus, we developed an objective scoring system to evaluate reliably CD44v6 (Bender Medsystems, Vienna, Austria) as a prognostic marker for prostate cancer.A total of 22 patients with metastatic stage pT3bN0M0 or any pTN1M0 disease and 18 with nonmetastatic disease less than stage pT3bN0M0 were selected from a well examined group of 114 who underwent radical retropubic prostatectomy. Mean followup was 33 months (range 4 to 78). A combined CD44v6 score was determined by adding the scores of the primary and secondary areas. CD44v6 expression in terms of the CD44v6 score in primary and metastatic tissues was examined. The relationships of CD44v6 expression with pathological stage, progression and PSA-free survival were also evaluated. The prognostic value of the CD44v6 score for progression was analyzed by multivariate analysis.Progression in the metastatic group was significantly higher than in the nonmetastatic group (p <0.0001). CD44v6 expression of the primary tumors differed significantly in the 2 groups (p = 0.014). The CD44v6 score in primary tumor tissues inversely correlated with pathological stage (p = 0.004) and progression (p = 0.035), and positively correlated with PSA-free survival (p = 0.041). Furthermore, patients in the nonmetastatic group with a CD44v6 score of greater than 75 (cutoff value) had a significantly better prognosis (log rank test p = 0.0022), while those with a CD44v6 score of less than 75 had a prognosis similar to those in the metastatic group. On multivariate analysis pathological stage and surgical margin positivity were independent factors for progression but the CD44v6 score was not.According to our results the suggested CD44v6 score system is useful. A CD44v6 score of less than 75 may be a predictor of poor prognosis in the nonmetastatic group and this property may have potential application for planning adjuvant therapy.
Human Pathology, 2009
Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in 11 cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Our study demonstrates the utility of immunohistochemical staining for CD44 in distinguishing prostatic small cell neuroendocrine carcinoma from its mimickers including prostatic adenocarcinoma of Gleason 5 pattern and small cell neuroendocrine carcinomas of other organs. CD44 is the first marker that shows a high degree of tissue/organ specificity for small cell neuroendocrine carcinomas. Because CD44 is a putative marker of prostate cancer stem cells, the strong and diffuse expression of CD44 and the lack of expression of prostate luminal differentiation markers androgen receptor and prostatic specific antigen in prostatic small cell neuroendocrine carcinomas suggest that the tumor cells may retain cancer stem cell features.
CD44 variant 6 is associated with prostate cancer metastasis and chemo‐/radioresistance
The Prostate, 2014
INTRODUCTIONProstate cancer (CaP) is the second leading malignancy in older men in Western countries. The role of CD44 variant 6 (CD44v6) in CaP progression and therapeutic resistance is still uncertain. Here, we investigated the roles of CD44v6 in CaP metastasis and chemo/radioresistance. Expression of CD44v6 in metastatic CaP cell lines, human primary CaP tissues and lymph node metastases was assessed using immunofluorescence and immunohistochemistry, respectively.METHODSKnock down (KD) of CD44v6 was performed in PC‐3M, DU145, and LNCaP cells using small interfering RNA (siRNA), and confirmed by confocal microscope, Western blot and quantitative real time polymerase chain reaction (qRT‐PCR). Cell growth was evaluated by proliferation and colony formation assays. The adhesive ability and invasive potential were assessed using a hyaluronic acid (HA) adhesion and a matrigel chamber assay, respectively. Tumorigenesis potential and chemo‐/radiosensitivity were measured by a sphere form...
Cell J, Vol 24, No 12, December , 2022
Objective: Expression of CD44 variant 6 (CD44v6) as a homing-associated cell adhesion molecule (HCAM), has proved to change most cancer cells. Aim of the study is the effect of mutant allele of CD44 (rs8193C>T) and Pum2 regulatory element as a prognosis factor of prostate neoplasms: a case-control and in silico studies in the Mazandaran province-Iran. Materials and Methods: In a case-control study, CD44-rs8193C>T genotyping of the 420 prostate neoplasms (210 benign prostatic hyperplasia (BPH) patients and 210 prostate cancer patients) and 150 healthy samples are performed by the touchdown polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. The T mutant allele effects on the mRNA structure and cell pathways were also investigated in silico methods. Results: Our results showed that the increase of T mutant allele frequency was significantly associated with BPH compared with prostate cancer. Furthermore, results showed TT genotype was significantly associated with BPH [odds ratio (OR)=0.572 and P=0.015], and also influenced the CD44v6 transcript secondary structure, miRNA binding, and regulatory element-binding site for Pum2 protein. Attachment of Pum2 to standard CD44 transcript may lead to transcript isoform-switching and shift-expression to a variety of CD44 isoforms, which can trigger some of the cell signaling pathways, such as Nanog-Stat, PKC-Nanog, and PKC-Twist. Conclusion: Based on this, the presence of the T mutant allele of CD44 (rs8193C>T) in the populations may create a regulatory element-binding site for Pum2. So, it could be known as a prognosis factor and prediction of prostate neoplasms. However, more comprehensive studies in different populations (with various ethnicities and large population sizes), and also CD44v6 gene expression studies in protein and transcript levels are required to confirm our data.