Godlewska Marlena, Arczewska Katarzyna D, Rudzińska Magdalena, Łyczkowska Anna, Krasuska Wanda, Hanusek Karolina, Ruf Jean, Kiedrowski Mirosław, Czarnocka Barbara
Department of Biochemistry and Molecular Biology, Center of Postgraduate Medical Education, Warsaw, Poland.
UMR-MD2, Aix-Marseille University, Marseille Medical School, Marseille, France.
PLoS One. 2017 Jun 2;12(6):e0179066. doi: 10.1371/journal.pone.0179066. eCollection 2017.
Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed.
In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs.
We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs.
Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.
甲状腺过氧化物酶(TPO)对甲状腺的生理功能至关重要。先前已证实乳腺癌患者中甲状腺过氧化物酶抗体(TPOAbs)的高患病率及其保护作用,表明乳腺癌与甲状腺自身免疫之间存在联系。最近,研究显示TPO存在于乳腺癌组织样本中,但其抗原性尚未得到分析。
在本研究中,我们使用一组特征明确的鼠抗人TPOAbs,研究了56例乳腺癌样本及其配对的正常(肿瘤周围)组织中TPO的表达水平及其抗原活性。
我们发现正常组织和癌组织样本中均存在TPO转录本,尽管后者的数量有所减少。此外,我们观察到在更晚期的癌症中TPO水平较低。在所有正常和癌组织样本中均证实了TPO蛋白的表达。我们还发现乳腺TPO中免疫显性区域(IDRs)的抗原性与甲状腺TPO相似,这对于与人类TPOAbs的有效相互作用至关重要。
TPO在乳腺癌中的表达及其抗原活性可能对TPOAb阳性的乳腺癌患者具有有益作用。然而,需要进一步研究以证实TPOAbs的有益作用并更好地理解其潜在机制。