LHRH receptor expression in sarcomas of bone and soft tissue

Abstract

Aim: Luteinizing hormone releasing hormone (LHRH) is a neurohormone, secreted by the hypothalamus, which regulates the secretion of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. LHRH acts by binding to receptors located in the pituitary gland. These receptors (LHRH receptors) have also been found in the cytoplasm of many tumor cells that involve both the reproductive and non-reproductive organs. These receptors have been demonstrated in prostate and breast cancers, endometrial carcinomas, renal cell carcinoma, lymphoma, carcinoma of liver, pancreas and skin. So far, the expression of LHRH receptors on sarcomas (i.e. malignant tumors of mesenchymal origin) has not been studied, except for endometrial sarcomas. It has also been demonstrated that both LHRH agonists and antagonists can down-regulate these receptors and thus inhibit these tumor cells. Another major therapeutic implication is that these receptors can be targeted specifically by peptides conjugated to anti-cancer drugs. The purpose of this study was to determine if LHRH receptors are expressed in primary and/or metastatic sarcomas of human origin. Methods: We looked at LHRH receptor expression in 38 consecutive sarcoma specimens, using immunohistochemistry. The specimens were either from office biopsy or from resected tumor; these were confirmed as sarcomas by histopathological examination. The receptor staining characteristics and the staining intensity were also documented. The pattern of staining was classified either as "focal or diffuse staining of the cytoplasm" and the intensity of staining was graded on a scale from 1+ to 4+. Results: Positive receptor staining was seen in 25 of the 38 (66%) specimens. Twelve of the specimens stained diffusely and 13 had focally positive staining. Three tumors had 1+ staining, 10 had 2+ staining, six had 3+ staining, and six tumors had 4+ staining. The tumors included undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, myofibroblastic sarcoma, myxofibrosarcoma, liposarcoma, dermatofibrosarcoma protuberans, metastatic chondrosarcoma and chordoma. Conclusion: Sarcomas express LHRH receptors with a varying incidence and degree. Our study suggests that those sarcomas that are LHRH receptor positive could potentially be treated with targeted chemotherapy.

A novel potential role of pituitary gonadotropins in the pathogenesis of human colorectal cancer

“…To address this issue, we focused our research on the effect of PtGs and studied, in addition to FSH, the effects of luteinizing hormone (LH) and prolactin (PRL) on colorectal cancer (CRC) cell lines. All of these PtGs are potent mitogens, and their role has already been associated with other human malignancies, including prostate [ 14 ], breast [ 15 ], lung [ 16 ], and ovarian cancer [ 17 ] as well as certain sarcomas [ 18 ].…”

Neonatal Hypoxic–Ischemic Encephalopathy: Perspectives of Neuroprotective and Neuroregenerative Treatments

“…[146][147][148] It has also been found in adrenal tissue and in breast and prostate cancer cells. 149 The presence of the receptor in other parts of the nervous system may be related with the neurotrophic role of GnRH. Treatment with GnRH or leuprolide acetate (LA), a GnRH agonist, favored the increase of outgrowths, and the length of neurites in studies with cell cultures of cortical neurons and spinal cord from rat embryos.…”

Bone Tumors: Types and Treatments

“…These receptors have also been found in the cytoplasm of many tumor cells that involve both reproductive and nonreproductive tissues. LH-RH agonists and antagonists have been found to downregulate these receptors and thus inhibit tumor growth [41]. Leuprolide acetate (Lupron, Eligard), goserelin acetate (Zoladex), triptorelin (Trelstar), and histrelin (Vantas) are some of the LH-RH agonists, whereas degarelix is an antagonist [4,40].…”

“…Leuprolide acetate (Lupron, Eligard), goserelin acetate (Zoladex), triptorelin (Trelstar), and histrelin (Vantas) are some of the LH-RH agonists, whereas degarelix is an antagonist [4,40]. LH-RHR can also be targeted specifically by peptides conjugated to anticancer drugs, thus developing cytotoxic analogs [41]. AN-152, commercially designated as AEZS-108, has been developed by conjugating 14-OH group of doxorubicin (DOX) to epsilon-amino group of D-Lys side chain of carrier peptide, through a glutaric acid spacer.…”

“…After internalization the drug is cleaved from the LH-RH moiety and accumulates in the nucleus. Because of receptor-mediated entry, the drug shows lesser side effects and also overcomes the resistance [41].…”