Autenshlyus A I, Studenikina A A, Bernado A V, Mikhailova E S, Proskura A V, Sidorov S V, Varaksin N A, Lyakhovich V V
Novosibirsk State Medical University, Novosibirsk, Russia; Institute of Molecular Biology and Biophysics, Novosibirsk, Russia.
Novosibirsk State Medical University, Novosibirsk, Russia.
Biomed Khim. 2019 Aug;65(5):418-423. doi: 10.18097/PBMC20196505418.
Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1β and the ratio of IL1β/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1β, as well as the ratio of IL1β/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.
在大多数情况下,乳腺癌是一种恶性肿瘤,与肿瘤浸润形成其微环境并产生各种细胞因子的细胞有关。本研究的目的是评估无特殊类型浸润性癌患者和乳腺良性疾病患者活检标本中肿瘤细胞及其微环境产生细胞因子的功能。为了评估肿瘤及其微环境产生细胞因子的活性,计算了多克隆激活剂对无特殊类型浸润性癌患者(I组)和乳腺良性肿瘤患者(II组)活检标本细胞因子产生的影响指数。II组进一步细分为IIa组,仅包括纤维腺瘤患者;IIb组,包括叶状纤维腺瘤、纤维腺病、纤维囊性乳腺病、导管内乳头状瘤病、硬化性腺病以及伴有微钙化的纤维囊性乳腺病患者。在肿瘤活检上清液中测量了IL-2、IL-6、IL-8、IL-10、IL-17、IL-18、IL-1β、IL-1Ra、TNF-α、IFN-γ、G-CSF、GM-CSF、VEGF和MCP-1的浓度。在比较I组和II组时,观察到良性疾病患者中多克隆激活剂对IL-17、IL-18和TNF-α产生的影响指数更高。与无特殊类型浸润性癌患者相比,纤维腺瘤患者中多克隆激活剂对IL-18、TNF-α和IL-1β产生的影响指数以及IL1β/IL1Ra的比值更高。I组和IIb组之间多克隆激活剂影响指数没有显著差异。这表明IIb组患者乳腺的变化与无特殊类型浸润性癌患者相似。与IIb组患者相比,IIa组患者中多克隆激活剂对IL-1β产生的影响指数以及IL1β/IL1Ra的比值更高。该研究结果确定了无特殊类型浸润性癌患者和乳腺良性肿瘤患者肿瘤活检标本产生细胞因子资源的特征。