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Sökning: WFRF:(Gil Jeovanis) > (2022) > Lipid Metabolic Rep...

Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer

Pirhonen, Juho (författare)
Minerva Foundation Institute for Medical Research,University of Helsinki
Szkalisity, Ábel (författare)
University of Helsinki,Minerva Foundation Institute for Medical Research
Hagström, Jaana (författare)
University of Helsinki,University of Turku
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Kim, Yonghyo (författare)
Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups,Korea Research Institute of Chemical Technology (KRICT)
Migh, Ede (författare)
Hungarian Academy of Sciences
Kovács, Mária (författare)
Hungarian Academy of Sciences
Hölttä, Maarit (författare)
Minerva Foundation Institute for Medical Research,University of Helsinki
Peränen, Johan (författare)
University of Helsinki
Seppänen, Hanna (författare)
Skåne University Hospital,University of Helsinki
Haglund, Caj (författare)
University of Helsinki
Gil, Jeovanis (författare)
Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Clinical Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Rezeli, Melinda (författare)
Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund
Malm, Johan (författare)
Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Department of Translational Medicine,Faculty of Medicine,Clinical Chemistry, Malmö,Lund University Research Groups
Horvath, Peter (författare)
Hungarian Academy of Sciences,Single-Cell Technologies Ltd.,University of Helsinki
Markó-Varga, György (författare)
Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups
Puolakkainen, Pauli (författare)
University of Helsinki
Ikonen, Elina (författare)
Minerva Foundation Institute for Medical Research,University of Helsinki
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 (creator_code:org_t)
2022
2022
Engelska 18 s.
Ingår i: Cancer Research. - 0008-5472. ; 82:21, s. 3932-3949
Relaterad länk:
http://dx.doi.org/10...
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignancies and potentially curable only with radical surgical resection at early stages. The tumor microenvironment has been shown to be central to the development and progression of PDAC.A better understanding of how early human PDAC metabolically communicates with its environment and differs from healthy pancreas could help improve PDAC diagnosis and treatment. Here we performed deep proteomic analyses from diagnostic specimens of operable, treatment-naive PDAC patients (n 14), isolating four tissue compartments by laser-capture microdissection: PDAC lesions, tumor-adjacent but morphologically benign exocrine glands, and connective tissues neighboring each of these compartments. Protein and pathway levels were compared between compartments and with control pancreatic proteomes. Selected targets were studied immunohistochemically in the 14 patients and in additional tumor microarrays, and lipid deposition was assessed by nonlinear label-free imaging (n = 16). Widespread downregulation of pancreatic secretory functions was observed, which was paralleled by high cholesterol biosynthetic activity without prominent lipid storage in the neoplastic cells. Stromal compartments harbored ample blood apolipoproteins, indicating abundant microvasculature at the time of tumor removal. The features best differentiating the tumor-adjacent exocrine tissue from healthy control pancreas were defined by upregulation of proteins related to lipid transport. Importantly, histologically benign exocrine regions harbored the most significant prognostic pathways, with proteins involved in lipid transport and metabolism, such as neutral cholesteryl ester hydrolase 1, associating with shorter survival. In conclusion, this study reveals prognostic molecular changes in the exocrine tissue neighboring pancreatic cancer and identifies enhanced lipid transport and metabolism as its defining features.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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