PhD Scientific Days 2020

Pathology and Oncology II. Posters

Autophagy Process in Relation to Mitochondria in Cholangiocarcinoma

Előadó neve

Szekerczés, Tímea, MSc

Előadó munkahelye

2nd Department of Pathology, Semmelweis University, Budapest

Előadó telefonszáma

06302945588

Előadó e-mail címe

szeki.timi@gmail.com

Az előadás címe

Autophagy Process in Relation to Mitochondria in Cholangiocarcinoma

Szerző(k) neve és munkahelye

Tímea Szekerczés1, Ildikó Illyés1, Milán Csengeri1, Krisztina Schlachter2, Klára Werling3, Erzsébet Szabó1, András Kiss1, Zsuzsa Schaff1, Gábor Lendvai1, Katalin Borka1
1 2nd Department of Pathology, Semmelweis University, Budapest
2 National Institute of Oncology, Center of Tumor Pathology, Department of Surgical and Molecular Pathology,
Budapest
3 2nd Department of Internal Medicine, Semmelweis University, Budapest

Szekció

Pathology and Oncology II. Posters

Language of the presentation

Hungarian

Section, first choice

Pathology and Oncology

Section, second choice

Molecular Sciences

Összefoglaló szövege

Autophagy eliminates damaged cellular organelles, including mitochondria, and macromolecules for recycling of bioenergetics components and it may act as a pro-survival mechanism to protect cancer cells from cellular stress. Furthermore, modulation of autophagy may sensitize cancer cells to chemotherapeutic agents. Our aim was to explore autophagy in cholangiocarcinoma (CC), as it is less frequently studied in CC as compared to hepatocellular carcinoma (HCC).Tissue microarrays were prepared from 70 CC [28 intrahepatic (iCC), 19 perihilar (pCC) and 23 distal (dCC)], 31 adjacent non-tumorous and 9 HCC tissues. TOMM20 and COX-4 was monitored by immunohistochemistry to characterize the mitochondria, beclin1, LC3, and p62 for demonstration of autophagy. Mann-Whitney test, Wilcoxon rank and Spearson’s rank test were applied along with Kaplan-Meier method for generating survival curves. In Huh28, TFK1 and HepG2 cells, mitochondrial morphology was detected by fluorescent dyes. Induction of autophagy was investigated by rapamycin, chemotherapy (5-FU, Cisplatin, Sorafenib) and/or autophagy inhibitor (chloroquin, CQ) treatments followed by Western blot. TOMM20, LC3 and p62 were elevated in iCC compared with surrounding tissues, whereas TOMM20 was more increased in eCC (pCC+dCC) as compared to iCC and HCC. Beclin1 showed higher levels in HCC than in iCC, and elevated p62 was found in iCC as compared with eCC. TOMM20 and COX4 showed a strong correlation in HCC (r=0.89), while LC3 had an association with grade in pCC (r=0.51). Higher TOMM20 was associated with a better survival in pCC, while higher beclin1 correlated with better prognosis in dCC. Mitochondrial staining revealed tubular distribution in HepG2, but HuH28, TFK1 showed disintegration of the mitochondrial network. LC3II/I was increased while p62 was decreased in HepG2 and Huh28 upon rapamycin and chemotherapy treatment compared with the controls. In TFK1, in contrast, neither LC3II/I was increased nor proliferation was different upon treatments. In conclusion, increased mitochondria volume and impaired autophagy was characteristic of iCC, whereas TOMM20 in pCC and beclin1 in dCC may be prognostic factors. Autophagy in intrahepatic tumor cells was rather inducible by rapamycin and chemotherapy, suggesting autophagy to be one of the strategies of chemotherapy resistance in these tumors.

Additional Information

Funding: This work was supported by grants from OTKA 108548 from the Hungarian National Research Foundation, and the ÚNKP-19-3-III-SE-1 New National Excellence Program of the Ministry for Innovation and Technology.

Supervisor: Zsuzsa Schaff email address: schaff.zsuzsa@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2245

Start

12:53

End

12:56

Authors (legacy)

Tímea Szekerczés1, Ildikó Illyés1, Milán Csengeri1, Krisztina Schlachter2, Klára Werling3, Erzsébet Szabó1, András Kiss1, Zsuzsa Schaff1, Gábor Lendvai1, Katalin Borka1
1 2nd Department of Pathology, Semmelweis University, Budapest
2 National Institute of Oncology, Center of Tumor Pathology, Department of Surgical and Molecular Pathology,
Budapest
3 2nd Department of Internal Medicine, Semmelweis University, Budapest