Expression of Receptors for Pituitary-Type Growth Hormone-Releasing Hormone (pGHRH-R) in Human Papillary Thyroid Cancer Cells: Effects of GHRH Antagonists on Matrix Metalloproteinase-2.
Papillary thyroid cancer (PTC) is the most prevalent of all endocrine cancers. In recent studies, the presence of receptors for pituitary-type growth hormone-releasing hormone (pGHRH-R) has been demonstrated in various human cancers, including human prostate, brain, and other cancer lines. Thyroid malignancies, however, have not yet been investigated in this regard. In this study, we found that pGHRH-R and its functional splice variant, SV1, are present in normal thyroid and PTC cells. We also treated seven normal and PTC tumor thyroid cells in vitro with a GHRH antagonist, MIA-602, to compare its anti-proliferation and anti-invasion potential against vehicle-treated cells. We found that treatment with GHRH antagonist increases the expression of SV1 and pGHRH-R in tumor cells compared to tumor cells exposed to vehicle only, a response which may alter the sensitivity of signaling kinases within the cells. GHRH antagonist treatment of tumor cells also reduced activity of the tumor invasion marker, matrix metalloproteinase (MMP)-2, compared to tumor cells exposed to vehicle only. The expression of pGHRH-R and SV1, as well as MMP-2 activity, in normal thyroid cells remained unaffected by GHRH antagonist treatment. Similarly, cell proliferation rates for tumor or normal thyroid cells were not affected by GHRH antagonist treatment. Our findings have important implications for the therapeutic use of GHRH antagonist in cases of aggressive PTC refractory to conventional treatment modalities, and in which protein expression and MMP-2 activity in normal thyroid tissue is left unaltered.
Laboratory on Sex and Gender Differences in Health and Disease, University of Miami Miller School of Medicine, 1550 NW 10th Avenue, Suite 411, Miami, FL, 33136, USA.
Paola
P
Catanuto
Jun
J
Tashiro
Ferenc G
FG
Rick
Patricia
P
Sanchez
Carmen C
CC
Solorzano
Marilyn K
MK
Glassberg
Norman L
NL
Block
John I
JI
Lew
Sharon J
SJ
Elliot
Andrew V
AV
Schally
D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D002291:Carcinoma, Papillary; D049109:Cell Proliferation; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D018013:Receptors, Neuropeptide / Q000096:biosynthesis*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000096:biosynthesis*; D017337:Sermorelin / Q000031:analogs & derivatives / Q000494:pharmacology; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism*
C550121:GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C048250:somatotropin releasing hormone receptor