ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment

Chi Lam Au-Yeung; Tsz Lun Yeung; Abhinav Achreja; Hongyun Zhao; Kay Pong Yip; Suet Ying Kwan; Michaela Onstad; Jianting Sheng; Ying Zhu; Dodge L. Baluya; Ngai Na Co; Angela Rynne-Vidal; Rosemarie Schmandt; Matthew L. Anderson; Karen H. Lu; Stephen T.C. Wong; Deepak Nagrath; Samuel C. Mok

doi:10.1038/s41467-020-17383-2

ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment

Chi Lam Au-Yeung, Tsz Lun Yeung, Abhinav Achreja, Hongyun Zhao, Kay Pong Yip, Suet Ying Kwan, Michaela Onstad, Jianting Sheng, Ying Zhu, Dodge L. Baluya, Ngai Na Co, Angela Rynne-Vidal, Rosemarie Schmandt, Matthew L. Anderson, Karen H. Lu, Stephen T.C. Wong, Deepak Nagrath, Samuel C. Mok

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23 Scopus citations

Abstract

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

Original language	English (US)
Article number	3546
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17383-2
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Au-Yeung, C. L., Yeung, T. L., Achreja, A., Zhao, H., Yip, K. P., Kwan, S. Y., Onstad, M., Sheng, J., Zhu, Y., Baluya, D. L., Co, N. N., Rynne-Vidal, A., Schmandt, R., Anderson, M. L., Lu, K. H., Wong, S. T. C., Nagrath, D., & Mok, S. C. (2020). ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment. Nature communications, 11(1), Article 3546. https://doi.org/10.1038/s41467-020-17383-2

Au-Yeung, CL, Yeung, TL, Achreja, A, Zhao, H, Yip, KP, Kwan, SY , Onstad, M, Sheng, J, Zhu, Y, Baluya, DL, Co, NN, Rynne-Vidal, A, Schmandt, R, Anderson, ML, Lu, KH, Wong, STC, Nagrath, D & Mok, SC 2020, 'ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment', Nature communications, vol. 11, no. 1, 3546. https://doi.org/10.1038/s41467-020-17383-2

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title = "ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment",

abstract = "Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin{\textquoteright}s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.",

author = "Au-Yeung, {Chi Lam} and Yeung, {Tsz Lun} and Abhinav Achreja and Hongyun Zhao and Yip, {Kay Pong} and Kwan, {Suet Ying} and Michaela Onstad and Jianting Sheng and Ying Zhu and Baluya, {Dodge L.} and Co, {Ngai Na} and Angela Rynne-Vidal and Rosemarie Schmandt and Anderson, {Matthew L.} and Lu, {Karen H.} and Wong, {Stephen T.C.} and Deepak Nagrath and Mok, {Samuel C.}",

note = "Funding Information: This study was supported in part by grants R01CA184918, R01CA227622, U01188388, The University of Texas MD Anderson Cancer Center Support Grant P30CA016672 from the National Institutes of Health; Wiegand Foundation and James B. & Lois R. Archer Charitable Foundation through the Center for Radiation Oncology Research; grants W81XWH-17-0126 and W81XWH-17-1-0146 from the Ovarian Cancer Research Program, Department of Defense; grant 318159 from the American Institute for Cancer Research; and T.T. & W.F. Chao Foundation and John S. Dunn Research Foundation. We thank MD Anderson{\textquoteright}s Department of Scientific Publications for providing editorial assistance. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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doi = "10.1038/s41467-020-17383-2",

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AU - Au-Yeung, Chi Lam

AU - Yeung, Tsz Lun

AU - Achreja, Abhinav

AU - Zhao, Hongyun

AU - Yip, Kay Pong

AU - Kwan, Suet Ying

AU - Onstad, Michaela

AU - Sheng, Jianting

AU - Zhu, Ying

AU - Baluya, Dodge L.

AU - Co, Ngai Na

AU - Rynne-Vidal, Angela

AU - Schmandt, Rosemarie

AU - Anderson, Matthew L.

AU - Lu, Karen H.

AU - Wong, Stephen T.C.

AU - Nagrath, Deepak

AU - Mok, Samuel C.

N1 - Funding Information: This study was supported in part by grants R01CA184918, R01CA227622, U01188388, The University of Texas MD Anderson Cancer Center Support Grant P30CA016672 from the National Institutes of Health; Wiegand Foundation and James B. & Lois R. Archer Charitable Foundation through the Center for Radiation Oncology Research; grants W81XWH-17-0126 and W81XWH-17-1-0146 from the Ovarian Cancer Research Program, Department of Defense; grant 318159 from the American Institute for Cancer Research; and T.T. & W.F. Chao Foundation and John S. Dunn Research Foundation. We thank MD Anderson’s Department of Scientific Publications for providing editorial assistance. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

AB - Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

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ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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