Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma

Berchtold, S; Grünwald, Barbara; Krüger, Achim; Reithmeier, Anja; Hähl, Teresa; Cheng, Tao; Feuchtinger, Annette; Born, Diana; Erkan, Mert; Kleeff, Jörg; Espósito, Irene

doi:10.1016/j.canlet.2014.10.020

Cited by 73 publications

(55 citation statements)

References 45 publications

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“…It is also likely that other microenvironment factors ( i.e. other cell types, ECM components, signaling molecules) play a role in collagen alignment that were not considered in our study, but remain active areas of research [18,19,25,32,43,50,62,85–95]. Taken together, quantification and further study of collagen alignment has the potential to provide additional, clinically-relevant information about PDAC tumors.…”

Section: Discussionmentioning

confidence: 95%

“…Stromal cells include fibroblasts, myofibroblastic pancreatic stellate cells (PSCs), endothelial cells, immune cells, adipose cells, and nerve cells. Key ECM components include fibrillar collagens [16–19], non-fibrillar collagens [20,21], fibronectin [22], periostin [23], tenascin-C [24,25], and others, all of which are aberrantly produced by cancer-associated fibroblasts (CAFs) and PSCs. As in many other solid tumor types, stromal biology has been shown to play a major role in PDAC progression by reciprocally interacting with cancer cells at all stages of the metastatic cascade, as well as by influencing therapeutic resistance [26–31].…”

Section: Introductionmentioning

confidence: 99%

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Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection

et al. 2016

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Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value. We hypothesized that the alignment of collagen is associated with PDAC patient survival. To address this, pathology-confirmed tissues from 114 PDAC patients that underwent curative-intent surgery were retrospectively imaged with Second Harmonic Generation (SHG) microscopy, quantified with fiber segmentation algorithms, and correlated to patient survival. The same tissue regions were analyzed for epithelial-to-mesenchymal (EMT), α-SMA, and syndecan-1 using complimentary immunohistostaining and visualization techniques. Significant inter-tumoral variation in collagen alignment was found, and notably high collagen alignment was observed in 12% of the patient cohort. Stratification of patients according to collagen alignment revealed that high alignment is an independent negative factor following PDAC resection (p = 0.0153, multivariate). We also found that epithelial expression of EMT and the stromal expression of α-SMA and syndecan-1 were positively correlated with collagen alignment. In summary, stromal collagen alignment may provide additional, clinically-relevant information about PDAC tumors and underscores the importance of stroma-cancer interactions.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection

et al. 2016

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“…The main form of COLI was generated by pancreatic stellate cells attributed to cancer cells in an indirect contactable desmoplastic area to activate TGF-β, while COLIV was produced by cancer cells themselves to form an autocrine loop in direct proximity to cancer cells, causing discontinuous basement membrane-like structures that interacted with the COLIV CB3 region and β1 integrin of the cancer cells [171]. However, another study showed that COLV was expressed by pancreatic stellate cells via paracrine loops in PDAC [172]. The desmoplastic reactions in primary cancer were divided into mature, intermediate, and immature based on the presence of keloid-like collagen and myxoid stroma; immature desmoplastic reactions were associated with higher T and N stages, more extensive liver metastasis, and higher recurrence rate than other reaction types [173].…”

Section: Subtype Of Mmps Associated Collagen Pathological Functions Omentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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“…Collagen type V is a fibrillar, regulatory collagen that is up-regulated in the TME and expressed by PaSCs. Similar to collagen type I, collagen type V over expression correlated with a malignant phenotype and promoted adhesion, migration and viability of various pancreatic cancer cell lines[102]. While the authors did not evaluate whether collagen type V over expression induced stem-like characteristics in the non-CSC population or activated the CSC compartment, it is likely that other ECM proteins can also modulate the plasticity of non-CSCs and CSCs, similar to that of collagen type I.…”

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confidence: 99%

Pancreatic cancer stem cells: A state or an entity?

Hermann

Sáinz

2018

Seminars in Cancer Biology

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Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, has a median overall survival of 6-12 months and a 5-year survival of less than 7%. While PDAC currently represents the 4th most frequent cause of death due to cancer worldwide, it is expected to become the second leading cause of cancer-related death by 2030. These alarming statistics are primarily due to both the inherent chemoresistant and metastatic nature of this tumor, and the existence of a subpopulation of highly plastic "stem"-like cells within the tumor, known as cancer stem cells (CSCs). Since their discovery in PDAC in 2007, we have come to realize that pancreatic CSCs have unique metabolic, autophagic, invasive, and chemoresistance properties that allow them to continuously self-renew and escape chemo-therapeutic elimination. More importantly, the concept of the CSC as a fixed entity within the tumor has also evolved, and current data suggest that CSCs are states rather than defined entities. Consequently, current treatments for the majority of PDAC patients are not effective, and do not significantly impact overall patient survival, as they do not adequately target the plastic CSC sub-population nor the transient/hybrid cells that can replenish the CSC pool. Thus, it is necessary that we improve our understanding of the characteristics and signals that maintain and drive the pancreatic CSC population in order to develop new therapies to target these cells. Herein, we will provide the latest updates and knowledge on the inherent characteristics of pancreatic CSCs and the CSC niche, specifically the cross-talk that exists between CSCs and niche resident cells. Lastly, we will address the question of whether a CSC is a state or an entity and discuss how the answer to this question can impact treatment approaches.

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Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma

Cited by 73 publications

References 45 publications

Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection

Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection

The role of collagen in cancer: from bench to bedside

Pancreatic cancer stem cells: A state or an entity?

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