Dinkel Zoë, Baker Adam, Akins Alannah, King Kylie L, Harrington Matthew, Kunkel Deborah, Gao Zhi, Ye Tong, Dunn Heather
Department of Bioengineering, Clemson University, Clemson, South Carolina, United States of America.
School of Mathematical and Statistical Sciences, Clemson University, Clemson, South Carolina, United States of America.
PLoS One. 2025 May 21;20(5):e0324655. doi: 10.1371/journal.pone.0324655. eCollection 2025.
This study evaluated collagen properties in TNBC samples collected from different racial groups to determine the presence of variance in matrix architecture. African American (AA) breast cancer patients have a significantly higher mortality rate and nearly a three-fold increased prevalence of triple negative breast cancer (TNBC) when compared to Caucasian (C) patients. The extracellular matrix region surrounding tumors contains abundant collagen fibers, and these fibers undergo remodeling throughout cancer progression, promote metastasis, and impede treatment response. High mammographic density, commonly known as dense breast tissue, is hypothesized to be more prevalent in AA women and characterized by increased collagen deposition and associated with more aggressive cancers. The aim of this research was to investigate fibrillar collagen architecture in TNBC samples from AA and C patients using two-photon microscopy with second harmonic generation (SHG), an intrinsic optical signal produced by fibrillar collagen. Twenty tissue regions per tumor sample were randomly selected for SHG microscopy, and image processing was conducted using the Fiji macro TWOMBLI to quantify mesoscopic fibrillar morphological properties and nanoscopic fibrillar properties with the Forward-Backward SHG ratio. Compared to the images from C tumor samples, those from AA samples exhibited a significant increase in parameters including fiber area, total length, and number of endpoints and branchpoints, but had decreased lacunarity. Collagen microstructure, including fibril arrangement and packing density, did not significantly differ between the groups. These results illustrate that the TNBC samples analyzed from AA patients may have macrostructural collagen characteristics associated with aggressive phenotype tumor formation.
本研究评估了从不同种族群体收集的三阴性乳腺癌(TNBC)样本中的胶原蛋白特性,以确定基质结构中是否存在差异。与白种人(C)患者相比,非裔美国(AA)乳腺癌患者的死亡率显著更高,三阴性乳腺癌(TNBC)的患病率几乎增加了两倍。肿瘤周围的细胞外基质区域含有丰富的胶原纤维,这些纤维在癌症进展过程中会发生重塑,促进转移,并阻碍治疗反应。乳腺钼靶密度高,通常称为致密乳腺组织,据推测在AA女性中更为普遍,其特征是胶原沉积增加,并与更具侵袭性的癌症相关。本研究的目的是使用双光子显微镜和二次谐波产生(SHG)技术,研究AA和C患者TNBC样本中的纤维状胶原蛋白结构,SHG是由纤维状胶原蛋白产生的一种固有光信号。每个肿瘤样本随机选择20个组织区域进行SHG显微镜检查,并使用Fiji宏TWOMBLI进行图像处理,以通过前后向SHG比率量化介观纤维形态学特性和纳米级纤维特性。与C肿瘤样本的图像相比,AA样本的图像在包括纤维面积、总长度以及端点和分支点数量等参数上显著增加,但孔隙度降低。两组之间的胶原蛋白微观结构,包括纤维排列和堆积密度,没有显著差异。这些结果表明,从AA患者分析的TNBC样本可能具有与侵袭性表型肿瘤形成相关的宏观结构胶原蛋白特征。