The thyroid status modulates the 4T1 breast cancer development in vivo through the regulation of cell proliferation, the composition of tumor microenvironment and the antitumor immune response

STERLE, H A; PAULAZO MA; AMORÓS M; HILDEBRANDT X; GARCÍA M; BOLONTRADE M; CREMASCHI, G A

Mar del Plata

Congreso; LXI Reunión anual SAIC, LXIV Reunión anual SAI, XLVIII Reunión anual SAFE, VII Reunión anual NANOMEDAR, V Congreso Nacional AACYTAL; 2016

SAIC, SAI, SAFE, NANOMEDAR, AACYTAL

The tumor development is regulated by a 􀁙ide range of factors,including hormones produced by the endocrine system. Ho􀁙ever,very little is 􀁍no􀁙n about the influence of thyroid hormone 􀀊TH􀀋levels on tumor gro􀁙th. 􀀲reviously 􀁙e sho􀁙ed that THs are ableto regulate the antitumor immune response. 􀀱ur aim 􀁙as to evaluatethe effect of thyroid status on the development of 􀀖T􀀓 breastcarcinoma in syngeneic mice. For this, 􀀤alb/c mice 􀁙ere treated􀁙ith thyroxine 􀀊􀀓􀀔mg/l􀀋 for 􀀕􀀒 days or propylthiouracil 􀀊􀀗􀀒􀀒mg/l􀀋for 􀀓􀀗 days in the drin􀁍ing 􀁙ater to obtain hyperthyroid 􀀊hyper􀀋 orhypothyroid 􀀊hypo􀀋 mice, respectively. 􀀯ice 􀁙ere then inoculateds.c 􀁙ith 􀀖T􀀓 cells.Hyper mice sho􀁙ed an increased tumor gro􀁙thrate 􀀊p􀀞􀀒.􀀒􀀗􀀋 compared to controls, 􀁙hile hypo mice bared tumors􀁙ith reduced volume 􀀊p􀀞􀀒.􀀒􀀗􀀋. The number of infiltrating immunecells 􀁙as similar in all groups. Ho􀁙ever, hyper tumors sho􀁙ed ahigher percentage of C􀀦􀀕􀀍 T cells 􀀊p􀀞􀀒.􀀒􀀗􀀋 and decreased 􀀯􀀦SC􀀊p􀀞􀀒.􀀒􀀗􀀋. Additionally, tumor draining lymph nodes of hypo micepresented increased C􀀦􀀖􀀍 􀀊p􀀞􀀒.􀀒􀀗􀀋 and C􀀦􀀚􀀍 􀀊p􀀞􀀒.􀀒􀀗􀀋 T cellspercentages and decreased C􀀦􀀓􀀛􀀍 cells 􀀊p􀀞􀀒.􀀒􀀗􀀋. 􀀱n the otherhand, spleens of hyper mice sho􀁙ed increased percentages of􀀯􀀦SC 􀀊p􀀞􀀒.􀀒􀀗􀀋 and 􀀰􀀭 cells 􀀊p􀀞􀀒.􀀒􀀗􀀋 even though the 􀀰􀀭 activity􀁙as decreased 􀀊p􀀞􀀒.􀀒􀀗􀀋 in this group.The composition of the tumormicroenvironment is also crucial to determine de tumor progression.To evaluate the effect of thyroid status on the migration ofmesenchymal stem cells 􀀊􀀯SC􀀋 cells to 􀀖T􀀓 tumors, 􀀯SC 􀁙ereobtained from murine bone marro􀁙, stained 􀁙ith 􀀦i􀀴, inoculated inthe tail vein of tumor􀀏bearing mice and analyzed by in vivo imaging.The results sho􀁙ed a decreased presence of 􀀯SC in hypertumors compared to control and hypo mice 􀀊p􀀞􀀒.􀀒􀀗􀀋.􀀱ur resultssuggest that the thyroid status modulates not only the proliferationof 􀀖T􀀓 cells but also the migration of 􀀯SC to the tumors andthe antitumor immune responses thus modifying tumor gro􀁙th.