Mechanical homeostasis is altered in uterine leiomyoma.
OBJECTIVE
Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells and lead to activation of Rho-dependent signaling and cell growth. Here we sought to determine whether the altered ECM that is produced by leiomyoma was accompanied by an altered state of mechanical homeostasis.


METHODS
We measured the mechanical response of paired leiomyoma and myometrial samples and performed immunogold, confocal microscopy, and immunohistochemical analyses.


RESULTS
Leiomyoma were significantly stiffer than matched myometrium. The increased stiffness was accompanied by alteration of the ECM, cell shape, and cytoskeleton in leiomyoma, compared with myometrial samples from the same uterus. Levels of AKAP13, a protein that is known to activate Rho, were increased in leiomyoma compared to myometrium. AKAP13 was associated with cytoskeletal filaments of immortalized leiomyoma cells.


CONCLUSIONS
Leiomyoma cells are exposed to increased mechanical loading and show structural and biochemical features that are consistent with the activation of solid-state signaling.
Rogers
Rebecca
R
Reproductive Biology and Medicine Branch, NICHD, NIH, Bethesda, MD 20892, USA.
Norian
John
J
Malik
Minnie
M
Christman
Gregory
G
Abu-Asab
Mones
M
Chen
Faye
F
Korecki
Casey
C
Iatridis
James
J
Catherino
William H
WH
Tuan
Rocky S
RS
Dhillon
Namisha
N
Leppert
Phyllis
P
Segars
James H
JH
D054758:A Kinase Anchor Proteins / Q000096:biosynthesis; D000328:Adult; D048708:Cell Growth Processes; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000378:metabolism* / Q000503:physiopathology; D018613:Microscopy, Confocal; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009215:Myometrium / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D014594:Uterine Neoplasms / Q000378:metabolism / Q000503:physiopathology; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D020742:rhoA GTP-Binding Protein