Soluble stroma‐related biomarkers of pancreatic cancer

Resovi, Andrea; Bani, Maria Rosa; Porcu, Luca; Anastasia, Alessia; Minoli, Lucia; Allavena, Paola; Cappello, Paola; Novelli, Francesco; Scarpa, Aldo; Morandi, Eugenio; Falanga, Anna; Torri, Valter; Taraboletti, Giulia; Belotti, Dorina; Giavazzi, Raffaella

doi:10.15252/emmm.201708741

Cited by 46 publications

(45 citation statements)

References 59 publications

(92 reference statements)

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“…MMP7 and MMP26 are the only two members of the matrilysin subfamily. A large number of studies have compared MMP7 expression in PDAC patients with pancreatitis patients and/or healthy controls and have consistently shown that MMP7 levels are elevated in PDAC patients (Table 1) [34][35][36]54,69,91,[97][98][99][100][101][102][103][104]. More importantly, MMP7 levels correlate with metastasis and/or survival in most, but not all, studies.…”

Section: Matrilysins In Pdacmentioning

confidence: 99%

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Slapak

Duitman

Tekin

et al. 2020

Biology

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Pancreatic cancer is a dismal disorder that is histologically characterized by a dense fibrotic stroma around the tumor cells. As the extracellular matrix comprises the bulk of the stroma, matrix degrading proteases may play an important role in pancreatic cancer. It has been suggested that matrix metalloproteases are key drivers of both tumor growth and metastasis during pancreatic cancer progression. Based upon this notion, changes in matrix metalloprotease expression levels are often considered surrogate markers for pancreatic cancer progression and/or treatment response. Indeed, reduced matrix metalloprotease levels upon treatment (either pharmacological or due to genetic ablation) are considered as proof of the anti-tumorigenic potential of the mediator under study. In the current review, we aim to establish whether matrix metalloproteases indeed drive pancreatic cancer progression and whether decreased matrix metalloprotease levels in experimental settings are therefore indicative of treatment response. After a systematic review of the studies focusing on matrix metalloproteases in pancreatic cancer, we conclude that the available literature is not as convincing as expected and that, although individual matrix metalloproteases may contribute to pancreatic cancer growth and metastasis, this does not support the generalized notion that matrix metalloproteases drive pancreatic ductal adenocarcinoma progression.

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Section: Matrilysins In Pdacmentioning

confidence: 99%

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Slapak

Duitman

Tekin

et al. 2020

Biology

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“…Six-to eight-week old female C57BL/6 mice (Charles River Laboratories, Lecco, Italy) were maintained under specific-pathogen-free conditions, with constant temperature and humidity, and handled using aseptic procedures. FC1199 cells (5 × 10 4 ) were implanted orthotopically in the pancreas as described [18]. Peptides were administered i.p.…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…Tumors were collected, fixed in 10% phosphate-buffered formalin, embedded in paraffin, and cut into 4 µm-thick sections. Sections were stained with Hematoxylin and Eosin (H&E) and Sirius red as described [18]. For immunohistochemical analysis of the tumor vasculature, anti-mouse CD31 antibody SZ31 (Dianova GmbH, Hamburg, Germany) followed by biotin-conjugated goat anti-rat IgG antibody (Vector Laboratories, Burlingame, CA, USA) and streptavidin-alkaline phosphatase conjugate were used [18].…”

Section: Histological and Immunohistochemical Analysismentioning

confidence: 99%

“…Sections were stained with Hematoxylin and Eosin (H&E) and Sirius red as described [18]. For immunohistochemical analysis of the tumor vasculature, anti-mouse CD31 antibody SZ31 (Dianova GmbH, Hamburg, Germany) followed by biotin-conjugated goat anti-rat IgG antibody (Vector Laboratories, Burlingame, CA, USA) and streptavidin-alkaline phosphatase conjugate were used [18]. CCN2 expression was evaluated using anti-CCN2 (ab6992, Abcam, Milano, Italy), followed by MACH 4 Universal HRP-Polymer (Biocare Medical, Pacheco, CA, USA) [18].…”

Section: Histological and Immunohistochemical Analysismentioning

confidence: 99%

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CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in Combination with Chemotherapy

Resovi

Borsotti

Ceruti

et al. 2020

Cells

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The prominent desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) is a determinant factor in tumor progression and a major barrier to the access of chemotherapy. The PDAC microenvironment therefore appears to be a promising therapeutic target. CCN2/CTGF is a profibrotic matricellular protein, highly present in the PDAC microenvironment and associated with disease progression. Here we have investigated the therapeutic value of the CCN2-targeting BLR100 and BLR200, two modified synthetic peptides derived from active regions of CCN3, an endogenous inhibitor of CCN2. In a murine orthotopic PDAC model, the two peptides, administered as monotherapy at low doses (approximating physiological levels of CCN3), had tumor inhibitory activity that increased with the dose. The peptides affected the tumor microenvironment, inhibiting fibrosis and vessel formation and reducing necrosis. Both peptides were active in preventing ascites formation. An increased activity was obtained in combination regimens, administering BLR100 or BLR200 with the chemotherapeutic drug gemcitabine. Pharmacokinetic analysis indicated that the improved activity of the combination was not mainly determined by the substantial increase in gemcitabine delivery to tumors, suggesting other effects on the tumor microenvironment. The beneficial remodeling of the tumor stroma supports the potential value of these CCN3-derived peptides for targeting pathways regulated by CCN2 in PDAC.

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“…Numerous potential biomarkers have been identi ed, including b7-h4, MUC13. However, none has been able to precisely predict the presence and outcomes of the disease, which is crucial in guiding the course of treatment of PAAD patients [8,9].…”

Section: Introductionmentioning

confidence: 99%

Expression of Spindle and Kinetochore-related Complex Subunit 3 is Associate With the Progression and Prognosis of Hepatocellular Carcinoma and Pancreatic Adenocarcinoma

Su¹,

Huang²,

Xie³

et al. 2020

Preprint

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Abstract Background Several studies have shown that Spindle and Kinetochore-related Complex Subunit 3 (SKA3) is closely related to the diagnosis and prognosis of various cancers. SKA3 plays a vital role in mitosis, but the mechanism underlying its action in tumors has not been fully elucidated. Methods Two separate microarrays of pancreatic adenocarcinoma (PAAD) and hepatocellular carcinoma (HCC) samples were downloaded from the Gene Expression Omnibus (GEO) and analyzed using R software. Tissues from 203 HCC and 321 PAAD patients were used for tissue microarray (TMA) construction and immunohistochemical staining for scoring. Kaplan-Meier estimators were used to determine their clinical relevance. Finally, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) were used for analyzed rich pathways of SKA3 to understand gene function further. Results Contrary to the results obtained from the GEO database, HCC and PAAD tumor tissues exhibited significantly lower expression of SKA3 compared to the adjacent tissues (P < 0.001). The size of HCC tumor and Edmondson grade were statistically correlated with SKA3 expression (P < 0.05). No correlation was observed between the levels of SKA3 expression and vascular invasion, metastasis, or lymphatic infiltration in HCC patients. Moreover, factors related to decreases of SKA3 in PAAD could similarly not be found. Kaplan-Meier survival curves indicated that SKA3 upregulation in HCC was significantly associated with better prognosis (P = 0.016). In contrast, low levels of SKA3 were related to poor prognosis of PAAD patients (P = 0.026). Enrichment analysis of GO and KEGG pathways showed that SKA3 gene was closely related to cell cycle pathways. Conclusions The results of the present study indicate that SKA3 expression can serve as a diagnostic and prognostic biomarker for HCC and PAAD. However, there is a need to conduct further studies to verify these findings, especially the prognostic role of SKA3 in PAAD.

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Soluble stroma‐related biomarkers of pancreatic cancer

Cited by 46 publications

References 59 publications

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in Combination with Chemotherapy

Expression of Spindle and Kinetochore-related Complex Subunit 3 is Associate With the Progression and Prognosis of Hepatocellular Carcinoma and Pancreatic Adenocarcinoma

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