Genetic and Expression Alterations in Association with the Sarcomatous Change of Cholangiocarcinoma Cells

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2009 Mar 17

PMID 19287191

Citations 33

Authors

Hee-Jung Yoo

Bo-Ra Yun

Jung-Hee Kwon

Hyuk-Soo Ahn

Min-A Seol

Mi-Jin Lee

Goung-Ran Yu

Hee-Chul Yu

BeeHak Hong

Kwanyong Choi

Dae-Ghon Kim

Affiliations

Soon will be listed here.

Abstract

Cholangiocarcinoma (CC) is an intrahepatic bile duct carcinoma with a high mortality rate and a poor prognosis. Sarcomatous change/epithelial mesenchymal transition (EMT) of CC frequently leads to aggressive intrahepatic spread and metastasis. The aim of this study was to identify the genetic alterations and gene expression pattern that might be associated with the sarcomatous change in CC. Previously, we established 4 human CC cell lines (SCK, JCK1, Cho-CK, and Choi-CK). In the present study, we characterized a typical sarcomatoid phenotype of SCK, and classified the other cell lines according to tumor cell differentiation (a poorly differentiated JCK, a moderately differentiated Cho-CK, and a well differentiated Choi-CK cells), both morphologically and immunocytologically. We further analyzed the genetic alterations of two tumor suppressor genes (p53 and FHIT) and the expression of Fas/FasL gene, well known CC-related receptor and its ligand, in these four CC cell lines. The deletion mutation of p53 was found in the sarcomatoid SCK cells. These cells expressed much less Fas/FasL mRNAs than did the other ordinary CC cells. We further characterize the gene expression pattern that is involved in the sarcomatous progression of CC, using cDNA microarrays that contained 18,688 genes. Comparison of the expression patterns between the sarcomatoid SCK cells and the differentiated Choi-CK cells enabled us to identify 260 genes and 247 genes that were significantly over-expressed and under-expressed, respectively. Northern blotting of the 14 randomly selected genes verified the microarray data, including the differential expressions of the LGALS1, TGFBI, CES1, LDHB, UCHL1, ASPH, VDAC1, VIL2, CCND2, S100P, CALB1, MAL2, GPX1, and ANXA8 mRNAs. Immunohistochemistry also revealed in part the differential expressions of these gene proteins. These results suggest that those genetic and gene expression alterations may be relevant to the sarcomatous change/EMT in CC cells.

Citing Articles

Proteogenomic characterisation of primary oral cancer unveils extracellular matrix remodelling and immunosuppressive microenvironment linked to lymph node metastasis.

Liu Y, Yang Z, Pu J, Zhong J, Khoo U, Su Y Clin Transl Med. 2025; 15(3):e70261.

PMID: 40038875 PMC: 11879901. DOI: 10.1002/ctm2.70261.

Loss of SMARCA4 induces sarcomatogenesis through epithelial-mesenchymal transition in ovarian carcinosarcoma.

Katayama Y, Iwasaki T, Yamamoto T, Shimada N, Nakashima M, Toya M Cancer Sci. 2024; 116(3):835-845.

PMID: 39716847 PMC: 11875775. DOI: 10.1111/cas.16423.

Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1.

Arif T, Shteinfer-Kuzmine A, Shoshan-Barmatz V Biomolecules. 2024; 14(10).

PMID: 39456237 PMC: 11506819. DOI: 10.3390/biom14101304.

Comparison of carcinosarcoma and adenocarcinoma of the gallbladder: a study based on SEER population for propensity matching and nomogram analysis.

Cao R, Jiang H, Zhang Y, Zhang W J Cancer Res Clin Oncol. 2023; 149(15):13985-13993.

PMID: 37543541 DOI: 10.1007/s00432-023-05220-0.

The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers.

Labat-de-Hoz L, Rubio-Ramos A, Correas I, Alonso M Cancers (Basel). 2023; 15(10).

PMID: 37345137 PMC: 10216460. DOI: 10.3390/cancers15102801.

References

Ito Y, Takeda T, Sasaki Y, Sakon M, Yamada T, Ishiguro S . Expression and clinical significance of the erbB family in intrahepatic cholangiocellular carcinoma. Pathol Res Pract. 2001; 197(2):95-100. DOI: 10.1078/0344-0338-00016. View

Goodman Z, Ishak K, Langloss J, Sesterhenn I, Rabin L . Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer. 1985; 55(1):124-35. DOI: 10.1002/1097-0142(19850101)55:1<124::aid-cncr2820550120>3.0.co;2-z. View

Savagner P, Yamada K, Thiery J . The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. J Cell Biol. 1997; 137(6):1403-19. PMC: 2132541. DOI: 10.1083/jcb.137.6.1403. View

Sarkar A, Yang P, Fan Y, Mu Z, Hauptmann R, Adolf G . Regulation of the expression of annexin VIII in acute promyelocytic leukemia. Blood. 1994; 84(1):279-86. View

Boyer B, Roche S, Denoyelle M, Thiery J . Src and Ras are involved in separate pathways in epithelial cell scattering. EMBO J. 1997; 16(19):5904-13. PMC: 1170221. DOI: 10.1093/emboj/16.19.5904. View

Kim D, Park S, You K, Lee G, Kim H, Moon W . Establishment and characterization of chromosomal aberrations in human cholangiocarcinoma cell lines by cross-species color banding. Genes Chromosomes Cancer. 2000; 30(1):48-56. DOI: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1053>3.0.co;2-p. View

Yamazaki T, Hibi K, Takase T, Tezel E, Nakayama H, Kasai Y . PGP9.5 as a marker for invasive colorectal cancer. Clin Cancer Res. 2002; 8(1):192-5. View

Levine A . The p53 tumor-suppressor gene. N Engl J Med. 1992; 326(20):1350-2. DOI: 10.1056/NEJM199205143262008. View

Thiagalingam S, Lisitsyn N, Hamaguchi M, Wigler M, WILLSON J, Markowitz S . Evaluation of the FHIT gene in colorectal cancers. Cancer Res. 1996; 56(13):2936-9. View

10.

Tusher V, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98(9):5116-21. PMC: 33173. DOI: 10.1073/pnas.091062498. View

11.

Oda Y, Katsuda S, Nakanishi I . An autopsy case of hepatic sarcomatoid tumor: immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma. Pathol Int. 1994; 44(3):230-6. DOI: 10.1111/j.1440-1827.1994.tb02597.x. View

12.

Hibi K, Westra W, Borges M, Goodman S, Sidransky D, Jen J . PGP9.5 as a candidate tumor marker for non-small-cell lung cancer. Am J Pathol. 1999; 155(3):711-5. PMC: 1866887. DOI: 10.1016/S0002-9440(10)65169-3. View

13.

Sozzi G, Alder H, Tornielli S, Corletto V, Baffa R, Veronese M . Aberrant FHIT transcripts in Merkel cell carcinoma. Cancer Res. 1996; 56(11):2472-4. View

14.

Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J . The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000; 2(2):84-9. DOI: 10.1038/35000034. View

15.

Wu W, Glinka A, Delius H, Niehrs C . Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/beta-catenin signalling. Curr Biol. 2001; 10(24):1611-4. DOI: 10.1016/s0960-9822(00)00868-x. View

16.

Kakizoe S, Kojiro M, Nakashima T . Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases. Cancer. 1987; 59(2):310-6. DOI: 10.1002/1097-0142(19870115)59:2<310::aid-cncr2820590224>3.0.co;2-s. View

17.

Ohta M, Inoue H, Cotticelli M, Kastury K, Baffa R, Palazzo J . The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell. 1996; 84(4):587-97. DOI: 10.1016/s0092-8674(00)81034-x. View

18.

Birchmeier C, Birchmeier W, Brand-Saberi B . Epithelial-mesenchymal transitions in cancer progression. Acta Anat (Basel). 1996; 156(3):217-26. DOI: 10.1159/000147848. View

19.

Ahrendt S, Nakeeb A, Pitt H . Cholangiocarcinoma. Clin Liver Dis. 2001; 5(1):191-218. DOI: 10.1016/s1089-3261(05)70161-6. View

20.

Mita E, Hayashi N, Iio S, Takehara T, Hijioka T, Kasahara A . Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem Biophys Res Commun. 1994; 204(2):468-74. DOI: 10.1006/bbrc.1994.2483. View