Expression of Cancer Stem Cell Markers OCT4 and CD133 in Transitional Cell Carcinomas

Sedaghat, S.; Gheytanchi, Elmira; Asgari, Mojgan; Roudi, Raheleh; Keymoosi, Hossein; Madjd, Zahra

doi:10.1097/pai.0000000000000291

Cited by 34 publications

(34 citation statements)

References 25 publications

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“…Of 140 bladder cancer samples, the majority of the bladder tumor cells (93%) expressed the OCT4 protein with various ranges of intensities and high OCT4 expression was observed in 28% of the population. OCT4 expression correlated with advanced stages of the tumor and factors associated with the stage including invasion status . Similarly, elevated ALDH1A1 expression levels are reported to correlate with advanced tumor grade and stage in bladder cancer .…”

Section: Discussionmentioning

confidence: 81%

“…OCT4 expression correlated with advanced stages of the tumor and factors associated with the stage including invasion status. 27 Similarly, elevated ALDH1A1 expression levels are reported to correlate with advanced tumor grade and stage in bladder cancer. 28,29 In addition, bladder cancer patients with high ALDH1A1 expression have higher recurrence and shorter survival rates than patients with low ALDH1A1 expression.…”

Section: Discussionmentioning

confidence: 98%

“…In bladder cancer, another CSC marker, octamer‐binding transcription factor 4 (OCT4) can be considered as a key regulator of tumor progression, aggressive behavior, and metastasis . Of 140 bladder cancer samples, the majority of the bladder tumor cells (93%) expressed the OCT4 protein with various ranges of intensities and high OCT4 expression was observed in 28% of the population.…”

Section: Discussionmentioning

confidence: 99%

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ALDH1A1 in patient‐derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression

Namekawa

Ikeda

Horie‐Inoue

et al. 2019

Intl Journal of Cancer

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Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long‐term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor‐initiating potential, or cancer stem‐like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CSC characterization will be the first step towards understanding the mechanisms underlying advanced disease. Here we generated long‐term patient‐derived cancer cells (PDCs) from bladder cancer patient specimens in spheroid culture, which is favorable for CSC enrichment. Pathological features of bladder cancer PDCs and PDC‐dependent patient‐derived xenografts (PDXs) were basically similar to those of their corresponding patients’ specimens. Notably, CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in PDCs. ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all‐trans RA could rescue ALDH1A1 shRNA‐suppressed spheroid formation. ALDH inhibitor also reduced the in vivo growth of PDC‐derived xenografts. ALDH1A1 knockdown study showed that tubulin beta III (TUBB3) was one of the downregulated genes in PDCs. We identified functional RA response elements in TUBB3 promoter, whose transcriptional activities were substantially activated by RA. Clinical survival database reveals that TUBB3 expression may associate with poor prognosis in bladder cancer patients. Moreover, TUBB3 knockdown was sufficient to suppress PDC proliferation and spheroid formation. Taken together, our results indicate that ALDH1A1 and its putative downstream target TUBB3 are overexpressed in bladder cancer, and those molecules could be applied to alternative diagnostic and therapeutic options for advanced disease.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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ALDH1A1 in patient‐derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression

Namekawa

Ikeda

Horie‐Inoue

et al. 2019

Intl Journal of Cancer

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“…Multiple studies, including from our group, have shown correlation between expression of NOTCH1, CD133, ALDH1A1, CD44 , and chemotherapy resistance, recurrence/prognosis . Further studies have correlated expression of CSC ( CD44, ALDH1A1, NOTCH1 ) and Epithelial Mesenchymal Transition (EMT) ( CADHERIN, TWIST, TGF‐βeta, MMPs) markers with the process of invasion and metastasis . Additionally, microenvironment is known to be a major player in maintaining CSC properties in different cancers .…”

Section: Introductionmentioning

confidence: 83%

“…12 Further studies have correlated expression of CSC (CD44, ALDH1A1, NOTCH1) and Epithelial Mesenchymal Transition (EMT) (CADHERIN, TWIST, TGF-βeta, MMPs) markers with the process of invasion and metastasis. [13][14][15] Additionally, microenvironment is known to be a major player in maintaining CSC properties in different cancers. [16][17][18] Factors released from cancer associated fibroblasts (CAF), such as chondroitin-sulfate, proteoglycan-serglycin, promotes tumor growth, invasion, migration and colonisation in breast and lung cancers in CD44-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cells and fibroblast niche cross talk in an in‐vitro oral dysplasia model

Kulsum

Raju²,

Raghavan³

et al. 2019

Molecular Carcinogenesis

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Understanding the cellular interactions during oral carcinogenesis has the potential to identify novel prognostic and therapeutic targets. This study aimed at investigating the cancer stem cell (CSC)‐fibroblast niche interactions using in‐vitro dysplastic cell line models developed from different stages of 4NQO‐induced oral carcinogenic mice model. The spontaneously transformed epithelial cells (DysMSCTR6, 14 and 16) were developed from three time points (mild/moderate/severe), while two fibroblast cell lines (FibroMSCTR12, 16) were developed from moderate and severe dysplastic tissue. The epithelial (Epcam+/Ck+) and the fibroblast cell lines (Vimentin+/α‐SMA+/Ck‐) were authenticated and assessment of cells representing progressive grades of dysplastic severity indicated a significant increase in dysplastic marker profile (P < 0.05). Evaluation of the CSC characteristics showed that an increase in expression of Cd133, Cd44, Aldh1a1, Notch1, and Sox2 was accompanied by an increase in migratory (P > 0.05) and colony formation capacity (P > 0.005). Targeting Notch1 (GSI inhibitor PZ0187; 30 μM), showed a significant reduction in cell proliferation capacity (P < 0.05) and in the dysplastic marker profile. Further, Notch1 inhibition resulted in down regulation of Cd133 and Aldh1a 1 (P < 0.05) and a complete abrogation of colony formation ability (P < 0.0001). The effect of niche interactions evaluated using FibroMSCTR12‐conditioned media studies, revealed an enrichment of ALDH1A1+ cells (P < 0.05), induction of spheroid formation ability (P < 0.0001) and increased proliferation capacity (3.7 fold; P < 0.005). Although PZ0187 reduced cell viability by ∼40%, was unable to abrogate the conditioned‐media induced increase in proliferation capacity completely. This study reports a Notch‐1 dependent enrichment of CSC properties during dysplastic progression and a Notch‐1 independent dysplastic cell‐fibroblast interaction during oral carcinogenesis.

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Genetic and molecular biology of bladder cancer among Iranian patients

Mojarrad

Moghbeli

2020

Molec Gen & Gen Med

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Background Bladder cancer (BC) is the sixth common cancer among Iranians. Various risk factors such as smoking, body mass index, chronic infection, age, and genetic factors are associated with BC progression. Methods It has been shown that a significant ratio of patients have tumors with muscle bladder layer invasion and poor prognosis at the time of diagnosis. Therefore, the early detection of tumors is required to reduce the mortality rate of BC cases. Since there is a wide geographical incidence variation in BC in Iran, it seems that the ethnic and genetic factors can be the main risk factors among Iranian BC patients. Results For the first time, in present review we have summarized all of the reported genes among Iranian BC patients until now which were significantly associated with tumorigenesis. Moreover, we categorized all of the reported genes based on their cell and molecular functions to clarify the genetic and molecular biology of BC among Iranian population. Conclusion This review paves the way of determination of a population‐based genetic panel markers for the early detection of BC in this population.

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Expression of Cancer Stem Cell Markers OCT4 and CD133 in Transitional Cell Carcinomas

Abstract: The correlation of OCT4, but not CD133, with the invasiveness of bladder cancer revealed that OCT4 can be considered as a key regulator of tumor progression, aggressive behavior, and metastasis; therefore, OCT4 can be a potential marker for targeted therapy of bladder cancer.

Cited by 34 publications

References 25 publications

ALDH1A1 in patient‐derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression

ALDH1A1 in patient‐derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression

Cancer stem cells and fibroblast niche cross talk in an in‐vitro oral dysplasia model

Genetic and molecular biology of bladder cancer among Iranian patients

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