Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology

Zhan, Hanxiang; Zhou, Bin; Cheng, Yugang; Xu, Jianwei; Wang, Lei; Zhang, Guangyong; Hu, Sanyuan

doi:10.1016/j.canlet.2017.01.041

Cited by 116 publications

(113 citation statements)

References 161 publications

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“…At the center of the tumor, nerves were scarce and the tissues in this area were fully replaced by desmoplastic stroma. Although tissues in both PDAC and CP were characterized by stromal reactions with marked fibrotic change, differences in the stromal composition between them were attributed to the interaction between pancreatic cancer cells and stromal cells, such as pancreatic stellate cells, cancer‐associated fibroblasts and macrophages . Their desmoplastic changes also differ macroscopically .…”

Section: Discussionmentioning

confidence: 99%

“…Although tissues in both PDAC and CP were characterized by stromal reactions with marked fibrotic change, differences in the stromal composition between them were attributed to the interaction between pancreatic cancer cells and stromal cells, such as pancreatic stellate cells, cancer-associated fibroblasts and macrophages. [27][28][29] Their desmoplastic changes also differ macroscopically. 30 Intrapancreatic nerves were also expected to interact with stromal cells as well as with cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma

Iwasaki

Hiraoka

Ino³

et al. 2019

Cancer Science

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Neural invasion is one of the malignant features contributing to locally advanced and/or metastatic disease progression in patients with pancreatic ductal adenocarcinoma ( PDAC ). Few studies exist on the distribution and state of nerve fibers in PDAC tissue and their clinicopathological impacts. The aim of the present study was to investigate the clinicopathological characteristics and prognostic value of intrapancreatic neural alterations in patients with PDAC . We retrospectively analyzed 256 patients with PDAC who underwent macroscopic curative surgery. Nerve fibers, immunolabeled with a specific neural marker GAP ‐43, were digitally counted and compared among PDAC , chronic pancreatitis ( CP ) and normal pancreatic tissues. Interlobular nerve fibers were apparently hypertrophic in both CP and PDAC , although intrapancreatic neural density and nerve number decreased characteristically in PDAC . They tended to decrease toward the center of the tumor. Kaplan‐Meier survival analyses revealed a statistically significant correlation between low neural density and shorter overall survival ( OS ) ( P = 0.014), and between high neural invasion and shorter OS ( P = 0.017). Neural density ( P = 0.04; HR = 1.496; 95% CI 1.018‐2.199) and neural invasion ratio ( P = 0.064; HR = 1.439; 95% CI .980‐2.114) were prognostic factors of shorter OS in the multivariate analysis. These findings suggest low intrapancreatic neural density in patients with PDAC as an independent prognosticator, which may represent aggressive tumor behavior. Furthermore, we propose a simple, practical and reproducible method (to measure neural density and the neural invasion ratio during conventional histopathological diagnosis of PDAC ), which has been validated using another cohort (n = 81).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma

Iwasaki

Hiraoka

Ino³

et al. 2019

Cancer Science

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“…Although it is still under debate whether depletion of stroma is protective or pathogenic [190], the stroma plays essential roles in promoting pancreatic cancer cell progression and determining response to therapy. In addition, several stroma-targeted therapies are already in clinical trials [191]. TGF-β is established as a key profibrotic cytokine, and the effects of TGF-β on stromal cells have been reviewed elsewhere [46].…”

Section: Induction Of Desmoplasia In Pancreatic Cancermentioning

confidence: 99%

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

et al. 2018

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Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

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“…Stromal cells are an important component of the tumor microenvironment (1). Tumor cells interplay with stromal cells and establish a variety of crosstalk mechanisms during tumor progression.…”

mentioning

confidence: 99%

“…Stromal cells, in turn, contribute to tumor growth and metastasis through various methods. One of the methods was supplying energy metabolites through aerobic glycolysis (1,2). Among stromal fibroblasts, an activated form is the cancer-associated fibroblast (CAF) (3).…”

mentioning

confidence: 99%

Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma

Jiang

Wang

et al. 2019

FASEB j.

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Metabolic reprogramming is a hallmark of cancer. Stromal cells could function as providers of energy metabolites for tumor cells by undergoing the “reverse Warburg effect,” but the mechanism has not been fully elucidated. The interaction between the tumoral microvesicles (TMVs) and stroma in the tumor microenvironment plays a critical role in facilitating cancer progression. In this study, we demonstrated a novel mechanism for the TMV‐mediated glycometabolic reprogramming of stromal cells. After being incubated with TMVs, normal human gingival fibroblasts exhibited a phenotype switch to cancer‐associated fibroblasts and underwent a degradation of caveolin 1 (CAV1) through the ERKl/2‐activation pathway. CAV1 degradation further induced the metabolic switch to aerobic glycolysis in the fibroblasts. The microvesicle‐activated fibroblasts absorbed more glucose and produced more lactate. The migration and invasion of oral squamous cell carcinoma (OSCC) were promoted after being cocultured with the activated fibroblasts. Fibroblast–cancer cell glycometabolic coupling ring mediated by monocarboxylate transporter (MCT) 4 and MCT1 was then proved in the tumor microenvironment. Results indicated a mechanism for tumor progression by the crosstalk between tumor cells and stromal cells through the reverse Warburg effect via TMVs, thereby identifying potential targets for OSCC prevention and treatment.—Jiang, E., Xu, Z., Wang, M., Yan, T., Huang, C, Zhou, X., Liu, Q., Wang, L., Chen, Y., Wang, H., Liu, K., Shao, Z., Shang, Z. Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma. FASEB J. 33, 5690–5703 (2019). http://www.fasebj.org

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Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology

Cited by 116 publications

References 161 publications

Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma

Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma

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