Stimulation of human arterial smooth muscle cell chondroitin sulfate proteoglycan synthesis by transforming growth factor-beta

1991 ◽  
Vol 27 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Jan-Kan Chen ◽  
Hiroyoshi Hoshi ◽  
Wallace L. McKeehan
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Chondroitin Sulfate Proteoglycan ◽  
Proteoglycan Synthesis ◽  
Sulfate Proteoglycan ◽  
Arterial Smooth Muscle Cell ◽  
Growth Factor Beta ◽  
Stimulation Of

Cell surface CD44-related chondroitin sulfate proteoglycan is required for transforming growth factor-beta-stimulated mouse melanoma cell motility and invasive behavior on type I collagen

1993 ◽  
Vol 105 (2) ◽  
pp. 501-511
Author(s):  
A.E. Faassen ◽  
D.L. Mooradian ◽  
R.T. Tranquillo ◽  
R.B. Dickinson ◽  
P.C. Letourneau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Chondroitin Sulfate ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Chondroitin Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Mouse Melanoma ◽  
Invasive Behavior ◽  
Growth Factor Beta

Tumor cell metastasis involves a complex series of events, including the adhesion, migration and invasive behavior of tumor cells on components of the extracellular matrix. Multiple cell surface receptors mediate interactions with the surrounding extracellular matrix and thereby influence cell adhesion, motility and invasion. We have previously described a cell surface CD44-related chondroitin sulfate proteoglycan on highly metastatic melanoma cells. CD44-chondroitin sulfate proteoglycan was shown to be important in melanoma cell motility and invasive behavior on type I collagen matrices. In our current studies, the role of cell surface CD44-chondroitin sulfate proteoglycan in collagen-mediated mouse melanoma cell migration and invasive behavior is further evaluated using transforming growth factor-beta 1. We report that transforming growth factor-beta 1 stimulates the migratory and invasive behavior of mouse melanoma cells on type I collagen. Transforming growth factor-beta 1 stimulated cell surface CD44-chondroitin sulfate proteoglycan synthesis in mouse melanoma cells, specifically through an upregulation of chondroitin sulfate production, while the expression of CD44-chondroitin sulfate proteoglycan core protein was not affected. Furthermore, transforming growth factor-beta 1-mediated enhancement of cell polarity, migration and invasive behavior on type I collagen gels was markedly inhibited in the presence of beta-D-xyloside, an agent that blocks chondroitin sulfate addition to the core protein. Collectively, our findings indicate that mouse melanoma cell surface CD44-chondroitin sulfate proteoglycan is required for transforming growth factor-beta 1-enhanced cell motility and invasion, and that CD44-chondroitin sulfate proteoglycan may play a role in forming and/or maintaining a dominant leading lamella, which is required for efficient locomotion.

scholarly journals Androgens Accentuate TGF‐β Dependent Erk/Smad Activation During Thoracic Aortic Aneurysm Formation in Marfan Syndrome Male Mice

2020 ◽  
Vol 9 (20) ◽  
Author(s):  
Yasushi Tashima ◽  
Hao He ◽  
Jason Z. Cui ◽  
Albert J. Pedroza ◽  
Ken Nakamura ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cell ◽  
Marfan Syndrome ◽  
Transforming Growth Factor Beta ◽  
Aortic Root ◽  
Transforming Growth Factor ◽  
Aneurysm Growth ◽  
Growth Factor Beta

Background Male patients with Marfan syndrome have a higher risk of aortic events and root dilatation compared with females. The role androgens play during Marfan syndrome aneurysm development in males remains unknown. We hypothesized that androgens potentiate transforming growth factor beta induced Erk (extracellular‐signal‐regulated kinase)/Smad activation, contributing to aneurysm progression in males. Methods and Results Aortic diameters in Fbn1 C1039G/+ and littermate wild‐type controls were measured at ages 6, 8, 12, and 16 weeks. Fbn1 C1039G/+ males were treated with (1) flutamide (androgen receptor blocker) or (2) vehicle control from age 6 to 16 weeks and then euthanized. p‐Erk1/2, p‐Smad2, and matrix metalloproteinase (MMP) activity were measured in ascending/aortic root and descending aorta specimens. Fbn1 C1039G/+ male and female ascending/aortic root‐derived smooth muscle cells were utilized in vitro to measure Erk/Smad activation and MMP‐2 activity following dihydrotestosterone, flutamide or transforming growth factor beta 1 treatment. Fbn1 C1039G/+ males have increased aneurysm growth. p‐Erk1/2 and p‐Smad2 were elevated in ascending/aortic root specimens at age 16 weeks. Corresponding with enhanced Erk/Smad signaling, MMP‐2 activity was higher in Fbn1 C1039G/+ males. In vitro smooth muscle cell studies revealed that dihydrotestosterone potentiates transforming growth factor beta‐induced Erk/Smad activation and MMP‐2 activity, which is reversed by flutamide treatment. Finally, in vivo flutamide treatment reduced aneurysm growth via p‐Erk1/2 and p‐Smad2 reduction in Fbn1 C1039G/+ males. Conclusions Fbn1 C1039G/+ males have enhanced aneurysm growth compared with females associated with enhanced p‐Erk1/2 and p‐Smad2 activation. Mechanistically, in vitro smooth muscle cell studies suggested that dihydrotestosterone potentiates transforming growth factor beta induced Erk/Smad activation. As biological proof of concept, flutamide treatment attenuated aneurysm growth and p‐Erk1/2 and p‐Smad2 signaling in Fbn1 C1039G/+ males.

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