Sjöstedt Evelina, Kolnes Anders J, Olarescu Nicoleta C, Mitsios Nicholas, Hikmet Feria, Sivertsson Åsa, Lindskog Cecilia, Øystese Kristin A B, Jørgensen Anders P, Bollerslev Jens, Casar-Borota Olivera
Department of Neuroscience, Karolinska Institutet, Solnavägen 1, 171 77 Solna, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjöldsväg 20, 752 37 Uppsala, Sweden.
Cancers (Basel). 2020 Dec 31;13(1):114. doi: 10.3390/cancers13010114.
Here, we report the investigation of transforming growth factor beta-receptor 3 like (TGFBR3L), an uncharacterised pituitary specific membrane protein, in non-neoplastic anterior pituitary gland and pituitary neuroendocrine tumours. A polyclonal antibody produced within the Human Protein Atlas project (HPA074356) was used for TGFBR3L staining and combined with SF1 and FSH for a 3-plex fluorescent protocol, providing more details about the cell lineage specificity of TGFBR3L expression. A cohort of 230 pituitary neuroendocrine tumours were analysed. In a subgroup of previously characterised gonadotroph tumours, correlation with expression of FSH/LH, E-cadherin, oestrogen (ER) and somatostatin receptors (SSTR) was explored. TGFBR3L showed membranous immunolabeling and was found to be gonadotroph cell lineage-specific, verified by co-expression with SF1 and FSH/LH staining in both tumour and non-neoplastic anterior pituitary tissues. TGFBR3L immunoreactivity was observed in gonadotroph tumours only and demonstrated intra-tumour heterogeneity with a perivascular location. TGFBR3L immunostaining correlated positively to both FSH ( = 0.290) and LH ( = 0.390) immunostaining, and SSTR3 ( = 0.315). TGFBR3L correlated inversely to membranous E-cadherin staining ( = -0.351) and oestrogen receptor β mRNA ( = -0.274). In conclusion, TGFBR3L is a novel pituitary gland specific protein, located in the membrane of gonadotroph cells in non-neoplastic anterior pituitary gland and in a subset of gonadotroph pituitary tumours.
在此,我们报告了对转化生长因子β受体3样蛋白(TGFBR3L)的研究,这是一种未被表征的垂体特异性膜蛋白,存在于非肿瘤性垂体前叶和垂体神经内分泌肿瘤中。利用人类蛋白质图谱计划(HPA074356)产生的多克隆抗体对TGFBR3L进行染色,并与SF1和FSH结合用于三重荧光方案,提供了关于TGFBR3L表达的细胞谱系特异性的更多细节。对230例垂体神经内分泌肿瘤进行了分析。在一组先前已表征的促性腺激素细胞肿瘤亚组中,探讨了其与FSH/LH、E-钙黏蛋白、雌激素(ER)和生长抑素受体(SSTR)表达的相关性。TGFBR3L显示膜性免疫标记,被发现是促性腺激素细胞谱系特异性的,通过在肿瘤和非肿瘤性垂体前叶组织中与SF1以及FSH/LH染色共表达得以验证。仅在促性腺激素细胞肿瘤中观察到TGFBR3L免疫反应性,并显示出肿瘤内异质性,位于血管周围。TGFBR3L免疫染色与FSH(r = 0.290)和LH(r = 0.390)免疫染色以及SSTR3(r = 0.315)呈正相关。TGFBR3L与膜性E-钙黏蛋白染色(r = -0.351)和雌激素受体β mRNA(r = -0.274)呈负相关。总之,TGFBR3L是一种新型的垂体特异性蛋白,位于非肿瘤性垂体前叶促性腺激素细胞的膜上以及一部分促性腺激素细胞垂体肿瘤中。