PANCREATIC CANCER


The most common – but unfortunately also most serious –  type of cancer in the pancreas is denoted pancreatic ductal adenoarcinoma. In this project, we aim at identifying and examining new molecular markers for this tumor type. The goal is to obtain a better understanding of how pancreatic ductal adenoarcinomas arise and grow. We have previously isolated the tumor cells by laser microdissection and analyzed them for mutations in the genes KRAS, BRAF and EGFR. We have also investigated markers of angiogenesis in this cancer form, and analyzed the expression pattern of the postulated stem cell markers CD133 and CD44 in normal and cancerous pancreatic tissue. Currently, we are working on how the genes ABO (determining blood type) and CEL (encoding a digestive enzyme) may be implicated in pancreatic cancer. We are also studying genetic alterations that are detectable in pancreatic juice.

 

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CD133 expression (brown) in normal pancreatic tissue.
The protein is expressed in acini centers and on the internal
surface of small ducts. The red area is an islet of Langerhans.

 

Fig

CD133 expression (brown) in pancreatic cancer. The
protein is strongly expressed on the internal surface
of duct-like structures formed by the cancer cells.

 

Participants/collaborators

Consultant/PhD Dag Hoem, Dept. of Surgery, Haukeland Univ. Hospital, Bergen
PhD fellow Khadija El Jellas, Dept. of Pathology, Haukeland Univ. Hospital, Bergen
PhD fellow Benedict Man Hung Choi, Dept. of Pathology, Haukeland Univ. Hospital, Bergen
Senior technician Solrun Steine, Gade Laboratory, UoBergen
Pathologists at the Dept. of Pathology, Haukeland Univ. Hospital, Bergen

Publications

El Jellas K, Hoem D, Hagen KG, Kalvenes MB, Aziz S, Steine SJ, Immervoll H, Johansson S, Molven A (2017). Associations between ABO blood groups and pancreatic ductal adenocarcinoma: influence on resection status and survival. Cancer Medicine 6: 1531-1540.

Dalva M, El Jellas K, Steine SJ, Ringdal M, Torsvik J, Immervoll H, Lerch MM, Johansson BB, Hoem D, Johansson S, Njølstad PR, Weiss U, Fjeld K & Molven A (2017). Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase (CEL) gene as risk factors in pancreatic cancer. Pancreatology 17: 83-88.

Calatayud D, Dehlendorff C, Boisen MK, Hasselby JP, Schultz NA, Werner J, Immervoll H, Molven A, Hansen CP & Johansen JS (2017). Tissue microRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers. Biomarker Research 5: 8.

Pettersen K, Andersen S, Degen S, Tadini V, Grosjean J, Hatakeyama S, Tesfahun AN, Moestue S, Kim J, Nonstad U, Romundstad PR, Skorpen F, Sørhaug S, Amundsen T, Grønberg BH, Strasser F, Stephens N, Hoem D, Molven A, Kaasa S, Fearon K, Jacobi C & Bjørkøy G (2017). Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling. Scientific Reports 7: 2046.

Dimcevski G, Kotopoulis S, Bjånes T, Hoem D, Schjøtt J, Gjertsen BT, Biermann M, Molven A, Sørbye H, McCormack E, Postema M & Gilja OH (2016). A human clinical trial using ultrasound and microbubbles to enhance treatment of inoperable pancreatic cancer. Journal of Controlled Release 243: 172-181.

Hoem D, Straume O, Immervoll H, Akslen LA & Molven A (2013). Vascular proliferation is associated with survival in pancreatic ductal adenocarcinoma. APMIS 121: 1037-1046.

Immervoll H, Hoem D, Steffensen OJ, Miletic H & Molven A (2011). Visualization of CD44 and CD133 in normal pancreas and pancreatic ductal adenocarcinomas: Non-overlapping membrane expression in cell populations positive for both markers. Journal of Histochemistry & Cytochemistry 59: 441-455.

Hoem D, Jensen D, Steine S, Thorsen TE, Viste A & Molven A (2008). Clinicopathological characteristics and non-adhesive organ culture of insulinomas. Scandinavian Journal of Surgery 97: 42-49.

Immervoll H, Hoem D, Sakariassen PØ, Steffensen OJ & Molven A (2008). Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer 8: 48.

Wang J, Sakariassen PØ, Tsinkalovsky O, Immervoll H, Bøe SO, Svendsen A, Prestegarden L, Røsland G, Thorsen F, Stuhr L, Molven A, Bjerkvig R & Enger PØ (2008). CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. International Journal of Cancer 122: 761-768.

Søreide K, Immervoll H & Molven A (2006). Pancreatic intraepithelial neoplasia – precursors to pancreatic cancer. Tidsskrift for Den Norske Lægeforening 126: 905-908. [in Norwegian]

Immervoll H, Hoem D, Kugarajh K, Steine S & Molven A (2006). Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: Lack of mutations in the BRAF and EGFR genes. Virchows Archiv  448: 788-796.