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The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence

Received: 28 October 2020     Accepted: 19 November 2020     Published: 30 November 2020
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Abstract

A novel pathogenesis of pulmonary lymphangioleiomyomatosis (PLAM) is presented incorporating a review of clinical and pathology research on the disease together with a review of research in the field of senescence. In this model of pathogenesis it is proposed that: 1) the primary site of origin for this disease is the Mullerian smooth muscle found in the female reproductive tract and this accounts for the striking female predominance of the disease; 2) the tumor spreads to the lungs via a mechanism similar to lymphangitic carcinomatosis and this accounts for its universal symmetric and bilateral distribution; 3) there is a mutational basis for a senescence-associated growth arrest which helps explain the absence of enlarging tumor masses in the lung despite years of disease duration; and 4) PLAM cells have a senescence-associated secretory phenotype with implications for the pathogenesis of the cystic transformation of the lungs. The secretory phenotype of PLAM cells is reviewed and the overlap with the senescence associated secretory phenotype products of known senescent cells is documented. The role of the switch to glycolytic metabolism (Warburg state) by PLAM cells is described. Finally, the “contradictory signals” hypothesis for the induction of the senescent state is explored and its role in PLAM described.

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 6, Issue 6)
DOI 10.11648/j.ijcems.20200606.16
Page(s) 136-148
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Pulmonary Lymphangioleiomyomatosis, Senescence-associated Secretory Phenotype, Senescence-associated Growth Arrest, Pathology, Pathogenesis

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Cite This Article
  • APA Style

    Charles Michael Lombard. (2020). The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence. International Journal of Clinical and Experimental Medical Sciences, 6(6), 136-148. https://doi.org/10.11648/j.ijcems.20200606.16

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    ACS Style

    Charles Michael Lombard. The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence. Int. J. Clin. Exp. Med. Sci. 2020, 6(6), 136-148. doi: 10.11648/j.ijcems.20200606.16

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    AMA Style

    Charles Michael Lombard. The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence. Int J Clin Exp Med Sci. 2020;6(6):136-148. doi: 10.11648/j.ijcems.20200606.16

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  • @article{10.11648/j.ijcems.20200606.16,
      author = {Charles Michael Lombard},
      title = {The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence},
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {6},
      number = {6},
      pages = {136-148},
      doi = {10.11648/j.ijcems.20200606.16},
      url = {https://doi.org/10.11648/j.ijcems.20200606.16},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20200606.16},
      abstract = {A novel pathogenesis of pulmonary lymphangioleiomyomatosis (PLAM) is presented incorporating a review of clinical and pathology research on the disease together with a review of research in the field of senescence. In this model of pathogenesis it is proposed that: 1) the primary site of origin for this disease is the Mullerian smooth muscle found in the female reproductive tract and this accounts for the striking female predominance of the disease; 2) the tumor spreads to the lungs via a mechanism similar to lymphangitic carcinomatosis and this accounts for its universal symmetric and bilateral distribution; 3) there is a mutational basis for a senescence-associated growth arrest which helps explain the absence of enlarging tumor masses in the lung despite years of disease duration; and 4) PLAM cells have a senescence-associated secretory phenotype with implications for the pathogenesis of the cystic transformation of the lungs. The secretory phenotype of PLAM cells is reviewed and the overlap with the senescence associated secretory phenotype products of known senescent cells is documented. The role of the switch to glycolytic metabolism (Warburg state) by PLAM cells is described. Finally, the “contradictory signals” hypothesis for the induction of the senescent state is explored and its role in PLAM described.},
     year = {2020}
    }
    

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  • TY  - JOUR
    T1  - The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence
    AU  - Charles Michael Lombard
    Y1  - 2020/11/30
    PY  - 2020
    N1  - https://doi.org/10.11648/j.ijcems.20200606.16
    DO  - 10.11648/j.ijcems.20200606.16
    T2  - International Journal of Clinical and Experimental Medical Sciences
    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
    SP  - 136
    EP  - 148
    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20200606.16
    AB  - A novel pathogenesis of pulmonary lymphangioleiomyomatosis (PLAM) is presented incorporating a review of clinical and pathology research on the disease together with a review of research in the field of senescence. In this model of pathogenesis it is proposed that: 1) the primary site of origin for this disease is the Mullerian smooth muscle found in the female reproductive tract and this accounts for the striking female predominance of the disease; 2) the tumor spreads to the lungs via a mechanism similar to lymphangitic carcinomatosis and this accounts for its universal symmetric and bilateral distribution; 3) there is a mutational basis for a senescence-associated growth arrest which helps explain the absence of enlarging tumor masses in the lung despite years of disease duration; and 4) PLAM cells have a senescence-associated secretory phenotype with implications for the pathogenesis of the cystic transformation of the lungs. The secretory phenotype of PLAM cells is reviewed and the overlap with the senescence associated secretory phenotype products of known senescent cells is documented. The role of the switch to glycolytic metabolism (Warburg state) by PLAM cells is described. Finally, the “contradictory signals” hypothesis for the induction of the senescent state is explored and its role in PLAM described.
    VL  - 6
    IS  - 6
    ER  - 

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Author Information
  • Department of Pathology, Stanford University School of Medicine, Stanford, California, the United States

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