Bitches with Mammary Tumors: the Role of Melatonin, Melatonin Receptor 1A and Tumor Apoptosis
DOI:
https://doi.org/10.22456/1679-9216.152811Keywords:
Apoptosis, dog, Ki-67, mammary tumor, melatoninAbstract
Background: Melatonin (N-acetyl-5-methoxytryptamine) is the main biologically active substance secreted by the pineal gland. The effects of melatonin depend on its binding to specific receptors in target tissues. Melatonin can directly affect tumor cells and affect their proliferation rates. Studies on canine mammary tumor cell cultures have reported that melatonin reduces cancer cells. Most of the physiological effects of melatonin are mediated by its interaction with 2 high-affinity G protein coupled rectors, termed melatonin receptors type 1 and type 2. Mammary tumors, most of which are malignant, are the most common neoplasms in intact bitches. Estimation of the proliferation potential of a tumor is useful for determining tumor malignancy. Also, Ki-67 is the preferred biomarker to determine proliferation and apoptosis in many types of canine mammary tumors.
Materials, Methods & Results: It was aimed at determining the difference in the amounts of melatonin (MEL) and melatonin receptor 1A (MTR1A) in the mammary tissues with different tumor types and to reveal its relationship with the tumor development mechanism, evaluating by apoptotic index (AI) and Ki-67 index. The study groups consisted of malignant epithelial tumors (Group MET; n=36) and hyperplasia & dysplasia (Group H&D; n=23). The samples were evaluated in 2 periods: Spring-Summer (SSP) (Group MET; n=23, Group H&D; n=7) and Autumn-Winter (AWP) (Group MET; n=13, Group H&D; n=16). MEL level in group MET was higher than in group H&D in both seasonal periods (P < 0.01). In Group MET, a significant rise in MEL level was observed in SPP than in AWP (P < 0.05). MTR1A level in group H&D was higher than in group MET in both seasonal periods (P < 0.05). In Group H&D, MTR1A level in SSP was higher than in AWP (P = 0.05). In Group MET, a significant rise in MTR1A level was observed in AWP than in SSP (P < 0.05). The Ki-67 index in Group MET was higher compared to group H&D in both seasonal periods (P < 0.001). In Group H&D, Ki-67 index in AWP was higher than in SSP (P < 0.001). In Group MET, a significant rise in Ki-67 index was observed in SSP than in AWP (P < 0.001). The AI value of the MET group tended to be higher than that of the H&D group (P = 0.07). In Group H&D, AI in AWP was higher than in SSP (P < 0.05). In Group MET, a significant rise in AI index was observed in SSP than in AWP (P < 0.05).
Discussion: Clinical similarities between human and canine mammary tumors (CMT) include age of onset, hormonal etiology, and disease course. In this respect, this study, which evaluated the amounts of Ki-67, AI, melatonin, and MTR1A in canine mammary tissue, serves as a role model for human breast cancer studies and provides important data, particularly regarding the amounts of endogenous melatonin and MTR1A in canine mammary tumor tissue. Ki-67 index values and endogenous melatonin concentrations were found to be higher in malignant epithelial tumors than in hyperplasia-dysplasia tumors, while AI values tended to be higher in malignant epithelial tumors. Furthermore, MTR1A concentrations were found to be higher in hyperplasia-dysplasia tumors than in malignant epithelial tumors. Overall, the findings indicate that endogenous melatonin levels and melatonin receptor expression are influenced by both seasonal rhythms and tumor biology; however, the role of melatonin within malignant mammary tissue appears to be a potential yet not fully elucidated modulatory effect.
Keywords: canine, apoptosis, dog, Ki-67, mammary tumor, melatonin.
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