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Lumican Exhibits Anti-Angiogenic Activity in a Context Specific Manner

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  • Published:
Cancer Microenvironment

Abstract

A series of overexpression studies have shown that lumican suppresses angiogenesis in tumors produced from pancreatic adenocarcinoma, fibrosarcoma, and melanoma tumor cells. Despite lumican’s anti-angiogenic activity, a clear correlation of differential expression of lumican in various cancers and cancer malignancy has failed to emerge. Therefore, we hypothesized that either 1.) endogenously expressed lumican is not anti-angiogenic or alternatively that 2.) lumican exhibits angiostatic activity only in limited microenvironments. Previously, lumican was shown to suppress tumor growth and angiogenesis in subcutaneously injected PanO2 pancreatic adenocarcinoma cells. Therefore, to determine if endogenously expressed lumican is anti-angiogenic we subcutaneously injected PanO2 cells into wild-type and lumican knockout mice and compared tumor growth and vascular densities of the resulting tumors. We found that tumors grown in lumican knockout animals were larger and contained significantly elevated vascular densities compared to those grown in wild-type mice. Interestingly however lumican knockout animals did not exhibit enhanced angiogenesis in aortic ring assays, matrigel plugs, or healing wound biopsies raising the possibility that lumican suppresses angiogenesis only in tumor microenvironments. To test this possibility, we sought a tumor model wherein lumican did not exhibit anti-angiogenic activity. Utilizing the 4T1 breast cancer model, we found that lumican suppressed 4T1 tumor growth and lung metastasis, but not angiogenesis. In conclusion, these results show that the angiostatic activity of lumican is dependent on currently undefined microenvironmental cues and therefore helps to understand why differential expression of lumican does not consistently correlate with human tumor malignancy.

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Acknowledgments

We are thankful to the NIH (Grant # 3R15CA133829-01A1S1 to ARA), and the INBRE program NIH Grant # P20 RR016454 (National Center for Research Resources) and # P20 GM103408 (National Institute of General Medical Sciences) for funding support. Thank you to Dr. Ken Cornell (Boise State University) for critical reading of the manuscript and excellent suggestions.

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Authors and Affiliations

  1. Department of Biology, Stanford University, Stanford, CA, 94305, USA

    Bikram Sharma

  2. Department of Biology, Indiana State University, Terre Haute, IN, 47805, USA

    Megan D. Ramus, Christopher T. Kirkwood & Emma E. Sperry

  3. First Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

    Pao-Hsien Chu

  4. Department of Ophthalmology, College of Medicine, Edith J. Crawley Vision Research Center, University of Cincinnati, Cincinnati, OH, 45267, USA

    Winston W. Kao

  5. Department of Biology, Boise State University, Boise, ID, 87205, USA

    Allan R. Albig

  6. Department of Biology, Boise State University, 1910 University Dr., Boise, ID, 83725-1515, USA

    Allan R. Albig

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  1. Bikram Sharma
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  2. Megan D. Ramus
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  3. Christopher T. Kirkwood
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  4. Emma E. Sperry
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  5. Pao-Hsien Chu
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  6. Winston W. Kao
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  7. Allan R. Albig
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Correspondence to Allan R. Albig.

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Sharma, B., Ramus, M.D., Kirkwood, C.T. et al. Lumican Exhibits Anti-Angiogenic Activity in a Context Specific Manner. Cancer Microenvironment 6, 263–271 (2013). https://doi.org/10.1007/s12307-013-0134-2

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  • DOI: https://doi.org/10.1007/s12307-013-0134-2

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