Prognostic Values of L-type Amino Acid Transporter 1 and CD98hc Expression in Breast Cancer

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2020 Sep 10

PMID 32907912

Citations 6

Authors

Masaaki Ichinoe

Tetuo Mikami

Nobuyuki Yanagisawa

Tsutomu Yoshida

Kiyomi Hana

Hitoshi Endou

Isao Okayasu

Norihiko Sengoku

Hideaki Ogata

Makoto Saegusa

Kazutoshi Shibuya

Yoshiki Murakumo

Affiliations

Soon will be listed here.

Abstract

Aims: L-type amino acid transporter 1 (LAT1) is a major Na-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.

Methods: LAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.

Results: High levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.

Conclusions: LAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

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References

Vona-Davis L, Rose D, Hazard H, Howard-McNatt M, Adkins F, Partin J . Triple-negative breast cancer and obesity in a rural Appalachian population. Cancer Epidemiol Biomarkers Prev. 2008; 17(12):3319-24. PMC: 4665096. DOI: 10.1158/1055-9965.EPI-08-0544. View

Kaira K, Oriuchi N, Imai H, Shimizu K, Yanagitani N, Sunaga N . Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in stage I pulmonary adenocarcinoma. Lung Cancer. 2009; 66(1):120-6. DOI: 10.1016/j.lungcan.2008.12.015. View

McGivan J, Pastor-Anglada M . Regulatory and molecular aspects of mammalian amino acid transport. Biochem J. 1994; 299 ( Pt 2):321-34. PMC: 1138275. DOI: 10.1042/bj2990321. View

Hafliger P, Graff J, Rubin M, Stooss A, Dettmer M, Altmann K . The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model. J Exp Clin Cancer Res. 2018; 37(1):234. PMC: 6150977. DOI: 10.1186/s13046-018-0907-z. View

Ichinoe M, Mikami T, Yoshida T, Igawa I, Tsuruta T, Nakada N . High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: comparison with non-cancerous lesions. Pathol Int. 2011; 61(5):281-9. DOI: 10.1111/j.1440-1827.2011.02650.x. View

CHRISTENSEN H . Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev. 1990; 70(1):43-77. DOI: 10.1152/physrev.1990.70.1.43. View

Yun D, Lee S, Park M, Kim J, Yu S, Park M . JPH203, an L-type amino acid transporter 1-selective compound, induces apoptosis of YD-38 human oral cancer cells. J Pharmacol Sci. 2014; 124(2):208-17. DOI: 10.1254/jphs.13154fp. View

Yanagisawa N, Ichinoe M, Mikami T, Nakada N, Hana K, Koizumi W . High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas. J Clin Pathol. 2012; 65(11):1019-23. DOI: 10.1136/jclinpath-2012-200826. View

Sakata T, Ferdous G, Tsuruta T, Satoh T, Baba S, Muto T . L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int. 2009; 59(1):7-18. DOI: 10.1111/j.1440-1827.2008.02319.x. View

10.

Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M . L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci. 2009; 101(1):173-9. PMC: 11158286. DOI: 10.1111/j.1349-7006.2009.01386.x. View

11.

Kim C, Cho S, Chun H, Lee S, Endou H, Kanai Y . BCH, an inhibitor of system L amino acid transporters, induces apoptosis in cancer cells. Biol Pharm Bull. 2008; 31(6):1096-100. DOI: 10.1248/bpb.31.1096. View

12.

Yanagida O, Kanai Y, Chairoungdua A, Kim D, Segawa H, Nii T . Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001; 1514(2):291-302. DOI: 10.1016/s0005-2736(01)00384-4. View

13.

Kaira K, Oriuchi N, Imai H, Shimizu K, Yanagitani N, Sunaga N . CD98 expression is associated with poor prognosis in resected non-small-cell lung cancer with lymph node metastases. Ann Surg Oncol. 2009; 16(12):3473-81. DOI: 10.1245/s10434-009-0685-0. View

14.

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

15.

Hayase S, Kumamoto K, Saito K, Kofunato Y, Sato Y, Okayama H . L-type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer. Oncol Lett. 2018; 14(6):7410-7416. PMC: 5755048. DOI: 10.3892/ol.2017.7148. View

16.

Lund M, Trivers K, Porter P, Coates R, Leyland-Jones B, Brawley O . Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat. 2008; 113(2):357-70. DOI: 10.1007/s10549-008-9926-3. View

17.

Toyoda M, Kaira K, Ohshima Y, Ishioka N, Shino M, Sakakura K . Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. Br J Cancer. 2014; 110(10):2506-13. PMC: 4021522. DOI: 10.1038/bjc.2014.178. View

18.

Satoh T, Kaira K, Takahashi K, Takahashi N, Kanai Y, Asao T . Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer. Anticancer Res. 2017; 37(2):631-636. DOI: 10.21873/anticanres.11357. View

19.

Kaira K, Oriuchi N, Imai H, Shimizu K, Yanagitani N, Sunaga N . l-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms. Cancer Sci. 2008; 99(12):2380-6. PMC: 11159766. DOI: 10.1111/j.1349-7006.2008.00969.x. View

20.

Kaira K, Sunose Y, Oriuchi N, Kanai Y, Takeyoshi I . CD98 is a promising prognostic biomarker in biliary tract cancer. Hepatobiliary Pancreat Dis Int. 2014; 13(6):654-7. DOI: 10.1016/s1499-3872(14)60278-2. View