The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence

Charles Michael Lombard

doi:doi:10.11648/j.ijcems.20200606.16

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The Pathogenesis of Pulmonary Lymphangioleiomyomatosis: A State of Neoplastic Senescence

Charles Michael Lombard

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 6, Issue 6)

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), 2024. Published by Science Publishing Group

Keywords

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

References

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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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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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Charles Michael Lombard

Department of Pathology, Stanford University School of Medicine, Stanford, California, the United States; Department of Pathology, El Camino Hospital, Mountain View, California, the United States

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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

Copy | Download

@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}
}

Copy | Download

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  -

Copy | Download