Matrix metalloproteinases and their endogenous regulators in squamous cervical carcinoma (review of the own data)

Solovуeva, N. I.; Timoshenko, O. S.; Ta, Gureeva; Kugaevskaya, E. V.

doi:10.18097/pbmc20156106694

Cited by 19 publications

(17 citation statements)

References 28 publications

(55 reference statements)

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“…ММП обладают определенной субстратной специфичностью, но в совокупности они гидролизуют все основные компоненты СТМ. Регуляторная функция ММП связана с активацией, инактивацией и модификацией свойств целого ряда биологически активных молекул [1,2,4,5]. ММП-1 относится к тканевым коллагеназам и является секретируемой, индуцируемой ММП, экспрессия которой в нормальных условиях практически не определяется.…”

Section: Introductionunclassified

“…ММП-1 относится к тканевым коллагеназам и является секретируемой, индуцируемой ММП, экспрессия которой в нормальных условиях практически не определяется. Индукция экспрессии ММП при плоскоклеточной карциноме шейки матки (ПКШМ) в опухоли происходит под действием онкогенов вирусов папиллом человека (HPV), а в прилегающей к опухоли нормальной ткани -под действием индуктора экспрессии ММП -EMMPRIN (CD147), который экспрессируется на поверхности опухолевых клеток [1][2][3][4][5][6][7]. Деградативная функция ММП-1 связана со специфической способностью запускать гидролиз фибриллярных коллагенов I, II, III, которые устойчивы к действию протеолитических ферментов.…”

Section: Introductionunclassified

“…ММП-1 гидролизует одну пептидную связь в молекуле коллагена. Образующиеся фрагменты в физиологических условиях подвергаются действию широкого спектра тканевых протеиназ, тем самым ММП-1 обеспечивает разрушение соединительнотканного барьера при развитии инвазивных процессов [1][2][3][4][5][6][7][8]. ММП-1 выполняет и важные регуляторные функции.…”

Section: Introductionunclassified

“…Исследования, проведенные нами на клетках, трансформированных онкогеном E7 HPV16, и линиях клеток карциномы шейки матки человека, трансформированных онкогенами вирусов папиллом человека 16 и 18 типов, показали, что основной вклад в инвазивный потенциал опухоли вносит увеличение экспрессии ММП-1 и ММП-9, в то время как экспрессия тканевых ингибиторов находится на чрезвычайно низком уровне или отсутствует. Получены предварительные данные об экспрессии ММП и их регуляторов не только в карциномах шейки матки, но и в прилегающей к опухоли нормальной ткани [4,[12][13][14]. В литературе данные по экспрессии ММП и их регуляторов в клинических образцах на протяжении от стенки влагалища до дна полости матки отсутствуют.…”

Section: Introductionunclassified

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Interstitial collagenase and their endogenous regulators in squamous cell cervical carcinoma

Timoshenko

Kugaevskaya

et al. 2017

BIOMED KHIM

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Interstitial collagenase (MMP-1) belongs to the family of matrix metalloproteinases (MMP), which play a key role in generalization processes of invasion and metastasis, which determine the degree of tumor malignancy. MMP-1 refers to secreted, inducible MMP, the expression of which in normal tissues is not defined. Induction of expression of MMP in CSS in the tumor occurs under the action of oncogenes of HPV, and in areas adjacent to the tumor normal tissue under the action of the inductor expression of MMP - EMMPRIN (CD147), which expressively on the surface of tumor cells. The aim of this study is to determine the possibility of expression ofMMP-1 and its regulators (tissue inhibitors TIMP-1 and activator - plasminogen activator - ADF) in morphologically normal body of the uterus during CSS. The study was carried out using on a tissue "tape" - postoperative specimens of the uterus when the diagnosis of CSS. All of the samples was expressed HPV16 gene E7. It was shown that: 1. The increase of MMP-1 expression, low expression (or lack thereof) of its inhibitors TIMP-1 and a very clear expression of the activator take place in the tumor when CSS that lead to increased activity of MMP-1, and aims to increase the destructive (invasive) potential of the tumor. 2. In morphologically normal tissue of the uterus during CSS the expression of MMP-1 can occur from the vaginal wall to the bottom of the uterine cavity, but at a much lower level than in the tumor. 3. These data indicate the possibility of development of a destructive process in morphologically normalnyh body tissues of the uterus during CSS, important for understanding the mechanism of tumor progression, and suggest participation in the process of expression of MMP-1 signaling by the type of epithelial-mesenchymal interaction .

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Section: Introductionunclassified

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Interstitial collagenase and their endogenous regulators in squamous cell cervical carcinoma

Timoshenko

Kugaevskaya

et al. 2017

BIOMED KHIM

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“…Solovyova N.I. with co-authors have shown that the main contribution to the invasive and metastatic potential of the squamous cell carcinoma of the cervix brings about an increase in the expression of collagenases of MMP-1 and MMP-14, of MMP-9 gelatinase and a decrease in the expression of TIMP-1 and -2 inhibitors [14]. This correlates with the results of other authors -the main role in the growth of invasive neoplastic cells in cervical cancer is played by matrix metalloproteinases (MMP) -1 and -2, the level of expression of which progresses with the growth of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Expression of MMP-9 as a Prognostic Factor of Uterine Sarcoma

et al. 2018

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Uterine sarcoma is a highly aggressive mesenchymal neoplasm with an extremely unfavorable prognosis. Up today there are still relevant issues concerning search for clinical-morphological and biomolecular criteria for prognosis relapse-free survival of uterine sarcoma patients. It is well-known, the increase of the expression level of MMP-9 in primary tumor or metastatic foci correlates with a low differentiation of tumor cells, high ability for invasiveness, high metastatic activity, and shortened life expectancy. It’s still unknown, whether it is possible to consider the expression of MMP-9 in uterine sarcoma cells as a convincing prognostic factor. For many types of epithelial malignant neoplasms, high metastatic rate is associated with an increase level of MMP-9 both in plasma and in tumor tissue. The purpose of this study is to investigate the features of MMP-9 expression in uterine sarcoma cells for development of the model for individual prediction of the disease course. The study of the surgical material of selected 54 cases of uterine sarcoma of stage I-II (according to FIGO criteria) with a known prognosis of the disease, which were distributed depending on the morphological type done: leiomyosarcoma (LMS) – 18 cases, endometrial stromal sarcoma (ESS) - 22 cases, undifferentiated sarcoma (US) – 14 (according to the classification of tumors of the uterus of the WHO). For histological examination, pieces of tissue were cut from different parts of the tumor nodes – central, peripheral, parts of the adjacent intact tissue of myometrium (total of 6-8 bits). The tumor cell phenotype was determined using low molecular weight cytokeratins (Cytokeratin PAN, AE1 / AE3), smooth muscle actin (Smooth Muscle Actin, 1A4), myogenin (Myogenin (F5D)), CD 10 and vimentin (Vimentin, V9). The histochemical label was evaluated in two parameters: the degree of prevalence and intensity of coloration. To assess the color intensity, a qualitative scale was used: 0 – no reaction, 1+ – weak cytoplasmic coloration to 30.0% of tumor cells, 2+ – moderate reaction, 30.0 to 60.0% of stained cells, 3+ – pronounced cytoplasmic reaction in 60,0-100,0% of tumor cells. Statistical processing of the data was performed using the “STATISTICA 10.0” program package. The conducted study has showed, the negative (0) and weak (1+) expression of matrix metalloproteinase-9 were observed in the most part of ESS and only partially in US. Despite the stage of the disease, with such a status of MMP-9, there was observed no signs of relapsed disease. The moderate (2+) and high (3+) expression of MMP-9 was detected in 44.5 % of uterine sarcoma, in the most part in LMS patients. However, if in LMS cases the progressive disease was observed only in one third of them (4 of 12 cases), in case of ESS and US, in all the patients with such tumors status there was observed relapsed disease. Such a reaction may be indicative for invasive and metastatic potential of ESS and US and cause of the hematogenous metastases.

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Interstitial collagenase MMP-1 and EMMPRIN in cell lines and in clinical specimens of cervical squamous cell carcinoma

et al. 2021

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Matrix metalloproteinases and their endogenous regulators in squamous cervical carcinoma (review of the own data)

Cited by 19 publications

References 28 publications

Interstitial collagenase and their endogenous regulators in squamous cell cervical carcinoma

Interstitial collagenase and their endogenous regulators in squamous cell cervical carcinoma

Expression of MMP-9 as a Prognostic Factor of Uterine Sarcoma

Interstitial collagenase MMP-1 and EMMPRIN in cell lines and in clinical specimens of cervical squamous cell carcinoma

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