Lysyl-Oxidase Dependent Extracellular Matrix Stiffness in Hodgkin Lymphomas: Mechanical and Topographical Evidence.
Lysyl-Oxidase Dependent Extracellular Matrix Stiffness in Hodgkin Lymphomas: Mechanical and Topographical Evidence.
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DOI：
10.3390/cancers14010259
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发表时间：
2022-01-05
期刊：
影响因子：
5.2
通讯作者：
Zocchi MR
中科院分区：
文献类型：
--
作者：
Alfano M;Locatelli I;D'Arrigo C;Mora M;Vozzi G;De Acutis A;Pece R;Tavella S;Costa D;Poggi A;Zocchi MR
细胞外基质（ECM）的组成和结构的改变，导致僵硬增加，是肿瘤发展、侵袭性和严重程度的条件。在这项研究中，我们报告了人类淋巴瘤的淋巴结（LN）硬度增加，通过LN弹性测量或通过生物标本的计算机成像来测量。僵硬度与淋巴瘤组织型和分级相符。赖基氧化酶（LOX）参与了霍奇金淋巴瘤中胶原交联的增加，而扫描电镜和偏振光显微镜显示的结构改变与晚期滤泡性淋巴瘤有关。基于这些数据，数字病理学可能有助于淋巴瘤的分期，赖氨酸氧化酶可能代表霍奇金淋巴瘤治疗的靶点。目的：已知细胞外基质（ECM）的生化组成和结构影响肿瘤的发展和侵袭性。为了阐明这一点，我们分析了霍奇金淋巴瘤（HL）、滤泡性淋巴瘤（FL）和弥漫性大b细胞淋巴瘤（DLBCL）的淋巴结（LN）的ECM刚度、胶原交联和各向异性，并与非肿瘤性LN （LDN）进行了比较。方法和结果：我们发现HL和晚期FL （3A级）比LDN、FL 1-2级和DLBCL的弹性（杨氏）模量增加。数字成像证实HL间质区较大，胶原交联增加；然后，通过扫描电子显微镜和偏振光显微镜观察到FL3A的结构变化和各向异性的增强。有趣的是，HL表达了高水平的赖氨酸氧化酶（LOX），一种负责胶原交联的酶。使用与非肿瘤组织相当的低弹性模量的明胶支架，我们证明HL ln来源的间充质基质细胞和HL细胞通过表达LOX增加了细胞外微环境的杨氏模量。事实上，β-氨基丙腈对LOX的抑制作用阻止了明胶硬度的增加。结论：这些数据表明，在人类淋巴瘤中可以检测到ECM不同的机械、地形和/或结构改变，并与其组织类型和分级有关。
Alterations of the composition and architecture of the extracellular matrix (ECM), leading to increased stiffness, is known to condition development, invasiveness and severity of neoplasms. In this study, we report increased lymph node (LN) stiffness in human lymphomas, measured by LN elastometry or by computerized imaging of bioptic specimens. Stiffness matched to lymphoma histotype and grading. The enzyme lysyl oxidase (LOX) is involved in the rise of collagen cross-linking in Hodgkin lymphomas, while altered architecture, shown by scanning electron microscopy and polarized light microscopy is involved in advanced follicular lymphomas. Based on these data, digital pathology may help in the staging of lymphomas, and lysyl oxidase may represent a target for therapy in Hodgkin lymphomas. Purpose: The biochemical composition and architecture of the extracellular matrix (ECM) is known to condition development and invasiveness of neoplasms. To clarify this point, we analyzed ECM stiffness, collagen cross-linking and anisotropy in lymph nodes (LN) of Hodgkin lymphomas (HL), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL), compared with non-neoplastic LN (LDN). Methods and Results: We found increased elastic (Young’s) modulus in HL and advanced FL (grade 3A) over LDN, FL grade 1–2 and DLBCL. Digital imaging evidenced larger stromal areas in HL, where increased collagen cross-linking was found; in turn, architectural modifications were documented in FL3A by scanning electron microscopy and enhanced anisotropy by polarized light microscopy. Interestingly, HL expressed high levels of lysyl oxidase (LOX), an enzyme responsible for collagen cross-linking. Using gelatin scaffolds fabricated with a low elastic modulus, comparable to that of non-neoplastic tissues, we demonstrated that HL LN-derived mesenchymal stromal cells and HL cells increased the Young’s modulus of the extracellular microenvironment through the expression of LOX. Indeed, LOX inhibition by β-aminopropionitrile prevented the gelatin stiffness increase. Conclusions: These data indicate that different mechanical, topographical and/or architectural modifications of ECM are detectable in human lymphomas and are related to their histotype and grading.
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影响因子：
14
作者：
Nichol, Jason W.;Koshy, Sandeep T.;Bae, Hojae;Hwang, Chang M.;Yamanlar, Seda;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
DOI：
10.3390/antiox10020312
发表时间：
2021-02-19
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Ferreira S;Saraiva N;Rijo P;Fernandes AS
通讯作者：
Fernandes AS
影响因子：
4.6
作者：
Nebuloni M;Albarello L;Andolfo A;Magagnotti C;Genovese L;Locatelli I;Tonon G;Longhi E;Zerbi P;Allevi R;Podestà A;Puricelli L;Milani P;Soldarini A;Salonia A;Alfano M
通讯作者：
Alfano M
影响因子：
4.4
作者：
Barnas, Jennifer L.;Simpson-Abelson, Michelle R.;Bankert, Richard B.
通讯作者：
Bankert, Richard B.
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM