Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer

Öhlund, Daniel; Lundin, Christina; Ardnor, B.; Öman, Mikael; Naredi, Peter; Sund, Malin

doi:10.1038/sj.bjc.6605107

Cited by 91 publications

(84 citation statements)

References 29 publications

(26 reference statements)

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“…This finding was unexpected as other studies had shown increased progression and poor survival in cases with high type IV collagen tissue expression (16,17,30). Our data were the result of a blinded evaluation of the type IV collagen expression.…”

Section: Nonmalignant Epithelium Invasive Frontcontrasting

confidence: 47%

“…As mentioned previously, the exact mechanism underlying the formation of the analyte is largely unknown. Previous studies have suggested that proteolysis and desmoplasia as a result of tissue remodeling are the responsible mechanisms (15,17). Patients with fibrotic and cirrhotic liver disorders also have increased levels of circulating type IV collagen (27,29), indicating that the mechanism for type IV collagen release is not exclusively cancer specific.…”

Section: Discussionmentioning

confidence: 99%

“…BIO82) was used for determination of circulating type IV collagen fragments (a1-chain fragments), which for the remainder of this paper will be referred to just as type IV collagen. The ELISA had been developed and validated for measurements of serum samples, and have been used in previously published studies (15)(16)(17)(27)(28)(29). Prior to use, we validated the assay for use of citrated plasma samples (Supplementary Data, Appendix S2).…”

Section: Type IV Collagen Determinationsmentioning

confidence: 99%

“…Each a-chain consists of an amino terminal 7S-domain, a long central triple-helical region and a carboxy-terminal noncollagenous domain-NC1 domain (14). An increase in the levels of circulating type IV collagen fragments were reported to be associated with the presence of malignant disease in patients with breast cancer (15), presence of liver metastases in colorectal cancer (16), and to be associated with poor prognosis in patients with pancreatic cancer (17). The proposed mechanism for the increase in circulating type IV collagen concentration was tumor-induced tissue remodeling through desmoplasia and proteolysis (17).…”

Section: Introductionmentioning

confidence: 99%

“…An increase in the levels of circulating type IV collagen fragments were reported to be associated with the presence of malignant disease in patients with breast cancer (15), presence of liver metastases in colorectal cancer (16), and to be associated with poor prognosis in patients with pancreatic cancer (17). The proposed mechanism for the increase in circulating type IV collagen concentration was tumor-induced tissue remodeling through desmoplasia and proteolysis (17). The desmoplastic stromal response to tumor formation is a common tumor feature and denotes the formation of collagen, formed as a result of recruitment and activation of stromal cells such as fibroblasts (18).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

Rolff

Christensen

Vainer

et al. 2016

Clinical Cancer Research

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Purpose: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer.Experimental Design: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries.Results: High levels of type IV collagen showed independent prognostic significance in both cohorts with hazard ratios (HRs; for a one-unit change on the log base 2 scale) of 2.25 [95% confidence intervals (CIs), 1.78-2.84; P < 0.0001] and 2.24 (95% CI, 1.75-2.86; P < 0.0001) for the training and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving and not receiving adjuvant antineoplastic therapy. However, in the validation set, the prognostic effect of the marker vanished when looking at patients who received adjuvant antineoplatic therapy (HR 0.90; 95% CI, 0.42-1.93) but was still present in the group not receiving adjuvant chemotherapy (HR 2.88; 95% CI, 1.98-4.21).Conclusions: The results indicate clinical validity of type IV collagen as a prognostic biomarker in colorectal cancer, although the suggested predictive role of the marker should be validated.

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Section: Nonmalignant Epithelium Invasive Frontcontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Type IV Collagen Determinationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

Rolff

Christensen

Vainer

et al. 2016

Clinical Cancer Research

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Novel prognostic markers within the CD44‐stromal ligand network in pancreatic cancer

Franklin

Billing

Öhlund

et al. 2018

The Journal of Pathology CR

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The dense stroma in pancreatic cancer tumours is rich in secreted extracellular matrix proteins and proteoglycans. Secreted hyaluronan, osteopontin and type IV collagen sustain oncogenic signalling by interactions with CD44s and its variant isoform CD44v6 on cancer cell membranes. Although well established in animal and in vitro models, this oncogenic CD44‐stromal ligand network is less explored in human cancer. Here, we use a pancreatic cancer tissue microarray from 69 primary tumours and 37 metastatic lymph nodes and demonstrate that high tumour cell expression of CD44s and, surprisingly, low stromal deposition of osteopontin correlate with poor survival independent of established prognostic factors for pancreatic cancer. High stromal expression of hyaluronan was a universal trait of both primary tumours and metastatic lymph nodes. However, hyaluronan species of different molecular mass are known to function differently in pancreatic cancer biology and immunohistochemistry cannot distinguish between them. Using gas‐phase electrophoretic molecular mobility analysis, we uncover a shift towards high molecular mass hyaluronan in pancreatic cancer tissue compared to normal pancreas and at a transcriptional level, we find that hyaluronan synthesising HAS2 correlates positively with CD44. The resulting prediction that high molecular mass hyaluronan would then correlate with poor survival in pancreatic cancer was confirmed in serum samples, where we demonstrate that hyaluronan >27 kDa measured before surgery is an independent predictor of postoperative survival. Our findings confirm the prognostic value of CD44 tissue expression and highlight osteopontin tissue expression and serum high molecular mass hyaluronan as novel prognostic markers in pancreatic cancer.

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Metabolic rewiring of pancreatic ductal adenocarcinoma: New routes to follow within the maze

Olivares

Vasseur

2015

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma (PDAC) is a debilitating and almost universally fatal malignancy. Despite advances in understanding of the oncogenetics of the disease, very few clinical benefits have been shown. One of the main characteristics of PDAC is the tumor architecture where tumor cells are surrounded by a firm desmoplasia. By reducing vascularization, thus both oxygen and nutrients delivery to the tumor, this stroma causes the appearance of hypoxic zones driving metabolic adaptation in surviving tumor cells in order to cope with challenging conditions. This metabolic reprogramming promoted by environmental constraints enhances PDAC aggressiveness. In this review, we provide a brief overview of previous works regarding the importance of glucose and glutamine addiction of PDAC cells. In particular we aim to highlight the need for exploring the impact of metabolites other than glucose and glutamine, such as non-essential amino acids and oncometabolites, to find new treatments. We also discuss the need for progress in methodology for metabolites detection. The overall purpose of our review is to emphasize the need to look beyond what is currently known, with a focus on amino acid availability, in order to improve our understanding of PDAC biology.Despite important scientific advances, pancreatic ductal adenocarcinoma (PDAC) remains a fatal cancer, offering one of the poorest prognosis and survival range.

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Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer

Cited by 91 publications

References 29 publications

The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

Novel prognostic markers within the CD44‐stromal ligand network in pancreatic cancer

Metabolic rewiring of pancreatic ductal adenocarcinoma: New routes to follow within the maze

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