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