Mempin Maria, Hu Honghua, Vickery Karen, Kadin Marshall E, Prince H Miles, Kouttab Nicola, Morgan John W, Adams William P, Deva Anand K
Surgical Infection Research Group, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA.
Cancers (Basel). 2021 Oct 22;13(21):5298. doi: 10.3390/cancers13215298.
Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a distinct malignancy associated with textured breast implants. We investigated whether bacteria could trigger the activation and multiplication of BIA-ALCL cells in vitro. BIA-ALCL patient-derived BIA-ALCL tumor cells, BIA-ALCL cell lines, cutaneous ALCL cell lines, an immortal T-cell line (MT-4), and peripheral blood mononuclear cells (PBMC) from BIA-ALCL, capsular contracture, and primary augmentation patients were studied. Cells were subjected to various mitogenic stimulation assays including plant phytohemagglutinin (PHA), Gram-negative bacterial lipopolysaccharide (LPS), Staphylococcal superantigens enterotoxin A (SEA), toxic shock syndrome toxin-1 (TSST-1), or sterilized implant shells. Patient-derived BIA-ALCL tumor cells and BIA-ALCL cell lines showed a unique response to LPS stimulation. This response was dampened significantly in the presence of a Toll-like receptor 4 (TLR4) inhibitor peptide. In contrast, cutaneous ALCL cells, MT-4, and PBMC cells from all patients responded significantly more to PHA, SEA, and TSST-1 than to LPS. Breast implant shells of all surface grades alone did not produce a proliferative response of BIA-ALCL cells, indicating the breast implant does not act as a pro-inflammatory stimulant. These findings indicate a possible novel pathway for LPS to promote BIA-ALCL cell proliferation via a TLR4 receptor-mediated bacterial transformation of T-cells into malignancy.
乳房植入物相关间变性大细胞淋巴瘤（BIA-ALCL）是一种与带纹理乳房植入物相关的独特恶性肿瘤。我们研究了细菌是否能在体外触发BIA-ALCL细胞的激活和增殖。研究了来自BIA-ALCL患者的BIA-ALCL肿瘤细胞、BIA-ALCL细胞系、皮肤ALCL细胞系、永生T细胞系（MT-4），以及来自BIA-ALCL、包膜挛缩和初次隆乳患者的外周血单个核细胞（PBMC）。对细胞进行了各种促有丝分裂刺激试验，包括植物血凝素（PHA）、革兰氏阴性菌脂多糖（LPS）、葡萄球菌超抗原肠毒素A（SEA）、中毒性休克综合征毒素-1（TSST-1）或经过消毒的植入物外壳。来自患者的BIA-ALCL肿瘤细胞和BIA-ALCL细胞系对LPS刺激表现出独特反应。在存在Toll样受体4（TLR4）抑制剂肽的情况下，这种反应显著减弱。相比之下，皮肤ALCL细胞、MT-4以及所有患者的PBMC细胞对PHA、SEA和TSST-1的反应比对LPS的反应明显更强。所有表面等级的乳房植入物外壳单独均未产生BIA-ALCL细胞的增殖反应，表明乳房植入物并非促炎刺激物。这些发现表明，LPS可能通过TLR4受体介导的T细胞细菌转化为恶性肿瘤，从而促进BIA-ALCL细胞增殖，这是一条可能的新途径。
