Mesenchymal reprogramming of adult human epithelial differentiation

Aboseif, Sherif R.; El‐Sakka, Ahmed I.; Young, Peter; Cunha, Gerald R.

doi:10.1046/j.1432-0436.1999.6520113.x

Cited by 92 publications

(63 citation statements)

References 28 publications

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“…Although morphologically similar to the epithelium in the renal pelvis and ureters, the urothelium of the urinary bladder and urethra is derived from the ventral urogenital sinus. The urogenital sinus is of endodermal origin 37,38 and PAX8 has not been detected in this area at any embryonic stages, which is consistent with the lack of PAX8 expression in the urothelium and urothelial carcinomas of the urinary bladder. Whether the urothelial carcinomas of the ureter may express PAX8 needs further investigation in large numbers of tumors from this area.…”

Section: Pax8 Expression In Normal and Neoplastic Renal Tissues G-x Tsupporting

confidence: 78%

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

et al. 2009

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Cell-lineage-specific transcription factors are a group of regulatory proteins expressed in embryonic, differentiated, or neoplastic cells of the same lineage and represent a valuable repertoire of tissue-specific markers for the diagnosis of human tumors. Together with PAX2, PAX8 is a nephric-lineage transcription factor and is required for the establishment of renal-lineage cells and the formation of the kidney. In contrast to PAX2, little is known about the expression of PAX8 in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8 in adult human kidney and renal epithelial tumors. We report here that PAX8 was detected in renal epithelial cells in all segments of renal tubules from the proximal tubules to the renal papillae and in the parietal cells of Bowman's capsule in the adult kidney. PAX8 was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8 was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8 was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8 was noted in some urothelial cells in the renal pelvis and ureters and B23% of urothelial carcinomas of the renal pelvis, but not in the urothelium or urothelial carcinomas of the urinary bladder; this probably underlines the different embryonic origins of urothelial cells in the upper and lower urinary tracts. As shown in this study, PAX8 is widely expressed in normal and neoplastic renal tissues. PAX8 may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.

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Section: Pax8 Expression In Normal and Neoplastic Renal Tissues G-x Tsupporting

confidence: 78%

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

et al. 2009

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“…It might also be plausible that the metastasised carcinoma cells upregulate LMO4 and LDB1 in the milieu of the lymph node. It is known that the local microenvironment modifies carcinoma cell differentiation (Aboseif et al, 1999;Liotta and Kohn, 2001). Further studies should be addressed to demonstrate a direct role for LMO4 and LDB1 in carcinoma metastasis.…”

Section: Discussionmentioning

confidence: 99%

The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity

et al. 2003

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Carcinoma cells can lose their epithelial cell characteristics and dedifferentiate into a fibroblast-like cell during progression of a neoplasm. Aberrant expression of oligomeric transcriptional complexes contributes to progression of carcinomas. Although individual transcription factors initiating progression remain unknown, LIM-only protein (LMO) and LIM-domain binding protein (LDB) negatively regulate breast carcinoma cell differentiation. In this study, we investigated the expression of LMO4 and LDB in squamous cell carcinomas of the oral cavity. LMO4 mRNA was amplified in four of six carcinoma tissues and eight of 12 carcinoma cell lines, and LDB1 in three carcinoma tissues and 11 cell lines examined. Immunoprecipitation studies revealed that LMO4 and LDB1 interact with each other in the nuclear milieu of the carcinoma cells indicating the presence of an LMO4-LDB1-mediated transcription complex. Both LMO4 and LDB1 proteins were preferentially localised in the nuclei of carcinoma cells at the invasive front and the immunoreactivity was increased in less-differentiated carcinoma tissues (Po0.01). Carcinoma cells metastasised to the cervical lymph nodes with increased immunoreactivity compared to the primary site of neoplasm (Po0.05). These data suggest that the LMO4 -LDB1 complexes may be involved in carcinoma progression possibly through dedifferentiation of squamous carcinoma cells of the oral cavity.

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“…It is generally accepted that physiological and malignant invasion use similar molecular mechanisms (Liotta et al, 1991). Cross-talk between mesenchyme and epithelium has been considered as a driver of differentiation and development (Aboseif et al, 1999;Nilsson and Skinner, 2001) and has been viewed as involved in the promotion of epithelial transformation (Aboseif et al, 1999;Olumi et al, 1999;Li et al, 2000). Altered cell-cell and cell-substratum signals may release normal tissue constraints, thereby enabling malignant cells to migrate across tissue boundaries (Liotta et al, 1991;Hanahan and Weinberg, 2000).…”

Section: Discussionmentioning

confidence: 99%

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

et al. 2009

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SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P ¼ 0.047 and P ¼ 0.014, respectively) and NAT lacking SNAI1 expression (P ¼ 0.054 and P ¼ 0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r ¼ 0.39; P ¼ 0.027) and inversely to CDH1 in NAT (r ¼ À0.46; P ¼ 0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

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Mesenchymal reprogramming of adult human epithelial differentiation

Cited by 92 publications

References 28 publications

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

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