CD10+fibroblasts are more involved in the progression of hilar/extrahepatic cholangiocarcinoma than of peripheral intrahepatic cholangiocarcinoma
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University and Institute for Cancer Pathology, National Kyushu Cancer Centre, Kyushu, Japan. Histopathology
(Impact Factor: 3.45).
10/2009; 55(4):423-31. DOI: 10.1111/j.1365-2559.2009.03398.x
To identify the role of CD10 expression of tumour-associated fibroblastic cells in the progression of cholangiocarcinoma (CC).
The CD10 expression of fibroblastic cells was investigated immunohistochemically in 167 cases of intrahepatic and extrahepatic CC and 29 cases of biliary dysplasia, comparing the clinicopathological parameters. CD10 expression of fibroblastic cells was observed in 5.7% (4/70) of peripheral intrahepatic CC, 29.2% (14/48) of hilar intrahepatic CC, and 57.1% (28/49) of extrahepatic CC. As for biliary dysplasia, CD10 expression of fibroblastic cells was observed in 4.3% (1/23) in the hepatic hilum and 20% (3/15) in the extrahepatic bile duct. CD10 expression had a strong relationship with the anatomical location of CC, and was more frequently detected in the periductal infiltrating type of hilar intrahepatic CC (P < 0.0001) and in less differentiated cases in extrahepatic CC (P = 0.0151). CD10 expression was observed more frequently in CC than in biliary dysplasia of hepatic hilum (P = 0.0365) and extrahepatic bile duct (P = 0.0262). CD10 expression was not a prognostic indicator in CC.
We suggest that CD10+ fibroblasts are more involved in the progression of hilar and extrahepatic CC than of peripheral intrahepatic CC.
Available from: José Mariano Ruiz de Almodóvar
- "However, despite the growing research interest in UCSSC biology, no precise study on their in situ identification has been reported to date. CD10 is a well-known biomarker of B-cell lymphomas , and its expression has also been reported in other cell types, including placental and bone marrow MSCs , and human fibroblasts . "
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ABSTRACT: It has been demonstrated that human umbilical cord stromal stem cells (UCSSCs) are bio-equivalent to bone marrow mesenchymal stem cells. However, little is known about their tissue origin or in vivo functions, and data on their expansion properties are limited due to early senescence in the culture methods described to date.
UC sections and cultured UCSSCs were analyzed with a panel of 12 antibodies. UCSSCs were grown in low-FCS containing medium at 5% or 21% oxygen and were assayed for their clonogenic properties, karyotype stability, expression of specific cellular markers, and multi-lineage potential. UCSSC contractile properties were evaluated by using collagen gel contraction assays under cytokine stimulus.
Immunohistochemistry studies showed that the UCSSCs were derived from the Wharton's jelly and not from the vascular smooth muscle sheath of the blood vessels. UCSSC growth properties were increased in a 5% oxygen atmosphere in comparison to normoxic culture conditions. In both culture conditions, UCSSCs were CD14-, CD34-, and CD45-negative while expressing high levels of CD73, CD90 and CD105 and maintaining their differentiation potentialities. UCSSCs expressed alpha smooth muscle actin and behaved as functional myofibroblasts when cellular contraction was challenged with appropriate stimuli.
UCSCs are mesenchymal stem cells that reside in the perivascular area of Wharton's jelly and are phenotypically and functionally related to myofibroblasts.
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ABSTRACT: The aim of this brief review is to provide an up-to-date view of the role played by α-smooth muscle actin-positive cancer-associated fibroblastic cells in promoting intrahepatic cholangiocarcinoma progression.
An increase in α-smooth muscle actin-positive cancer-associated fibroblastic cells in the stroma of intrahepatic cholangiocarcinoma has recently been demonstrated to accelerate cholangiocarcinoma progression. However, our understanding of the evolving cellular and molecular interactions between these stromal cells and cholangiocarcinoma cells in relation to promoting intrahepatic cholangiocarcinoma progression is only just beginning to be elucidated. Imbalances in multifactorial growth factor/cytokine signaling, activation of Hedgehog-GLI signaling and of proteases involved in extracellular matrix remodeling, and matricellular protein-protein and protein-cholangiocarcinoma cell interactions, as well as hypoxia, all appear to factor into the complex and dynamic interactive mechanisms through which cancer-associated fibroblastic cells crosstalk with cholangiocarcinoma cells to promote intrahepatic cholangiocarcinoma progression. Novel three-dimensional organotypic co-culture models are being developed to facilitate relevant studies of cancer-associated fibroblastic cell/cholangiocarcinoma cell interactions that may more accurately mimic physiologically pertinent features of the tumor.
Increasing our understanding of critical interactive pathways by which cancer-associated fibroblastic cells crosstalk with cholangiocarcinoma cells to promote tumor progression can lead to the development of novel multitargeting strategies for intrahepatic cholangiocarcinoma therapy.
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ABSTRACT: Tumor-stromal fibroblasts have recently been reported to play important roles in the tumor progression of cancer in various organs. The purpose of the present study was to investigate whether any characteristic histologic features of tumor-stromal fibroblasts could accurately predict the outcome of 318 patients with invasive ductal carcinoma of the breast who had received neoadjuvant therapy. We observed a small number of tumor-stromal fibroblasts with characteristic nuclear features existing in the tumor stroma and named these cells "atypical tumor-stromal fibroblasts." We then assessed the absence or presence of atypical tumor-stromal fibroblasts in biopsy (taken before neoadjuvant therapy) and surgical (taken after neoadjuvant therapy) materials and analyzed the outcome predictive powers of the presence of atypical tumor-stromal fibroblasts in biopsy and surgical materials using multivariate analyses that included well-known clinicopathological factors. The multivariate analyses demonstrated that the presence of atypical tumor-stromal fibroblasts assessed using biopsy materials had significantly higher hazard ratios for tumor recurrence and tumor-related death in patients with nodal metastasis and also significantly higher hazard ratios for tumor recurrence and tumor-related death independent of the hormone receptor status of the tumors. The results of this study clearly indicated that the presence of atypical tumor-stromal fibroblasts, especially in biopsy materials, is significantly associated with tumor recurrence and the tumor-related death of patients with invasive ductal carcinoma of the breast who have received neoadjuvant therapy.
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