Gram-Negative Bacterial Lipopolysaccharide Promotes Tumor Cell Proliferation in Breast Implant-Associated Anaplastic Large-Cell Lymphoma

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.

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Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report

Journal of Hematology and Oncology Research ◽

10.14302/issn.2372-6601.jhor-21-3733 ◽

2021 ◽

Vol 4 (1) ◽

pp. 28-34

Author(s):

Kumkum Vadehra ◽

Jennifer Cai ◽

Rashmi Rekha Bhuyan ◽

Ping Ji ◽

Rose Venegas ◽

...

Keyword(s):

Tumor Cells ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Breast Implant ◽

Fluid Collection ◽

Breast Implants ◽

Large Cell ◽

Silicone Implants ◽

Axillary Lymph ◽

Large Cell Lymphoma

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.

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Abstract 3669: Autocrine interleukin/STAT3 signaling in breast implant-associated T cell anaplastic large cell lymphoma cell lines suggests a mechanism for tumor progression and effective therapy

10.1158/1538-7445.am2012-3669 ◽

2012 ◽

Author(s):

Connor H. Church ◽

Melissa G. Lechner ◽

Carolina Megiel ◽

Rikki S. Bass ◽

Sarah M. Russell ◽

...

Keyword(s):

T Cell ◽

Tumor Progression ◽

Cell Lines ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Breast Implant ◽

Large Cell ◽

Lymphoma Cell ◽

Stat3 Signaling ◽

Large Cell Lymphoma

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cJun Is Phosphorylated at Ser73 and Contributes to Cell Cycle Progression in Anaplastic Large Cell Lymphoma.

Blood ◽

10.1182/blood.v106.11.2620.2620 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2620-2620

Author(s):

Vassiliki Leventaki ◽

Elias Drakos ◽

Francois-Xavier Claret ◽

L. Jeffrey Medeiros ◽

George Z. Rassidakis

Keyword(s):

Cell Cycle ◽

Tumor Cells ◽

Cell Lines ◽

Anaplastic Large Cell Lymphoma ◽

Cell Cycle Progression ◽

Cell Lymphoma ◽

Large Cell ◽

S Phase ◽

Cycle Progression ◽

Large Cell Lymphoma

Abstract Anaplastic Large Cell Lymphoma (ALCL) frequently carries the t(2;5)(p23;q35) or variant translocations resulting in overexpression of anaplastic lymphoma kinase (ALK). cJun is a member of the activator protein-1 (AP-1) family, which is a group of transcription factors that control cell proliferation, differentiation, growth and apoptosis. The activity of cJun can be regulated by phosphorylation at serine 73 (Ser73) and serine 63 (Ser63) residues of the N-terminal domain. It is believed that cJun promotes cell cycle progression, in part, through downregulation of the cyclin-dependent kinase inhibitor p21. Previous studies have shown high AP-1 activity and cJun overexpression in Hodgkin lymphoma and ALCL (Mathas et al, EMBO J2002; 21:4104). In this study, we assessed for expression of cJun and its Ser73- and Ser63-phosphorylated forms in two ALK+ (Karpas 299 and SU-DHL-1) and one ALK- (Mac2A) ALCL cell lines by western blot analysis, and in 31 ALCL tumors (15 ALK+, 16 ALK-) by immunohistochemistry using tissue microarrays and specific antibodies. To examine the role of cJun in cell survival and proliferation in our in vitro system, ALCL cells were transiently transfected with small interfering RNA (siRNA) specific for cJun. Cell viability, proliferation of viable cells and cell cycle progression from G1 to S-phase were assessed by trypan blue exclusion, MTS and BrdU assays, respectively. All three ALCL cell lines expressed total cJun and Ser73-phosphorylated cJun (Ser73p-cJun) at a high level, whereas Ser63-phosphorylated cJun was expressed at a low level. In addition, all 31 ALCL tumors expressed total cJun in most neoplastic cells. Ser73p-cJun was also detected in all ALCL tumors at a variable level with the percentage of Ser73p-cJun-positive tumor cells ranging from 5% to 95%. By contrast, Ser63p-cJun was detected rarely in tumor cells. Transient transfection of ALCL cells with specific siRNA resulted in almost complete silencing of total cJun expression and absence of Ser73p-cJun expression, which was associated with decreased cell viability and a substantial (40%) decrease of cell growth. cJun silencing also resulted in cell cycle arrest as shown by decreased S-phase fraction. These cell cycle changes were associated with a marked increase of p21 levels and downregulation of cyclin D2 and D3. In conclusion, cJun is highly phosphorylated at serine 73 in ALCL cell lines and tumors and may contribute to cell cycle progression. Targeting cJun expression or phosphorylation using gene therapy approaches may represent a novel therapeutic strategy for patients with ALCL.

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Optimizing Breast Pocket Irrigation: The Breast Implant–Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) Era

Aesthetic Surgery Journal ◽

10.1093/asj/sjz246 ◽

2019 ◽

Vol 40 (6) ◽

pp. 619-625 ◽

Cited By ~ 4

Author(s):

Eric J Culbertson ◽

Christina Felder-Scott ◽

Anand K Deva ◽

David E Greenberg ◽

William P Adams

Keyword(s):

Anaplastic Large Cell Lymphoma ◽

Antimicrobial Agents ◽

Cell Lymphoma ◽

Breast Implant ◽

Capsular Contracture ◽

Large Cell ◽

Gram Negative ◽

Recommendations For Practice ◽

Large Cell Lymphoma ◽

Antimicrobial Effectiveness

Abstract Background Specific antimicrobial breast pocket irrigations have been proven over the past 20 years to reduce the incidence of capsular contracture by a factor of 10, and the emergence of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) and its link to bacteria/technique has created renewed interest in different antimicrobial breast pocket preparation agents. Our previous studies have identified that both Betadine-containing and non-Betadine-containing antimicrobial irrigations provide excellent broad-spectrum bacterial coverage. The current science of BIA-ALCL has implicated the Gram-negative microbiome as a key in pathogenesis. Objectives The aim of this study was to revisit the antimicrobial effectiveness of clinically utilized Betadine and non-Betadine solutions, along with other antimicrobial agents that have not yet been tested, against multiple organisms, including additional common Gram-negative bacteria associated with chronic breast implant infections/inflammation. Methods Current and new antimicrobial breast irrigations were tested via standard techniques for bactericidal activity against multiple Gram-positive and Gram-negative strains. Test results are detailed and clinical recommendations for current antimicrobial irrigations are provided. Results Betadine-containing irrigations were found to be superior according to the testing performed. Conclusions There are quite few misconceptions with regard to antimicrobial breast pocket irrigation. These are discussed and final evidence-based recommendations for practice are given.

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Migration Properties Distinguish Tumor Cells of Classical Hodgkin Lymphoma from Anaplastic Large Cell Lymphoma Cells

Cancers ◽

10.3390/cancers11101484 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1484

Author(s):

Olga Goncharova ◽

Nadine Flinner ◽

Julia Bein ◽

Claudia Döring ◽

Emmanuel Donnadieu ◽

...

Keyword(s):

Cell Motility ◽

Hodgkin Lymphoma ◽

Tumor Cells ◽

Cell Lines ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Receptor Expression ◽

Classical Hodgkin Lymphoma ◽

Large Cell Lymphoma

Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.

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