Breast cancer–Related lymphedema results in impaired epidermal differentiation and tight junction dysfunction Journal Article
| Authors: | Campbell, A. C.; Baik, J. E.; Sarker, A.; Brown, S.; Park, H. J.; Kuonqui, K. G.; Shin, J.; Pollack, B. L.; Roberts, A.; Ashokan, G.; Rubin, J.; Kataru, R. P.; Dayan, J. H.; Barrio, A. V.; Mehrara, B. J. |
| Article Title: | Breast cancer–Related lymphedema results in impaired epidermal differentiation and tight junction dysfunction |
| Abstract: | Breast cancer–related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of FLG and the tight junction protein ZO-1 in skin affected by moderate lymphedema or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to those in the controls (areas without backflow and from the unaffected arm). In vitro stimulation of keratinocytes with lymph fluid obtained from patients undergoing lymphedema surgery led to the same changes as well as increased expression of keratin 14, a marker of immature keratinocytes. Finally, using mouse models of lymphedema, we showed that similar to the clinical scenario, the expression of skin barrier proteins was decreased relative to that in normal skin and that colonization with Staphylococcus epidermidis bacteria amplified this effect as well as lymphedema severity. Taken together, our findings suggest that lymphatic fluid stasis contributes to skin barrier dysfunction in lymphedema. © 2024 The Authors |
| Keywords: | adult; clinical article; controlled study; human tissue; protein expression; aged; middle aged; unclassified drug; human cell; nonhuman; pathophysiology; lymph node dissection; mouse; animal; metabolism; animals; mice; animal tissue; skin biopsy; epidermis; animal experiment; animal model; cell differentiation; in vitro study; pathology; breast neoplasms; keratinocyte; lymphedema; disease model; tight junction; disease severity; breast tumor; bacterial colonization; cytokeratin 14; disease models, animal; cell stimulation; keratinocytes; postoperative pain; tissue differentiation; lymph; etiology; isoflurane; lymph flow; complication; protein zo1; buprenorphine; lymphatics; lymphography; procedures; tight junctions; zonula occludens-1 protein; indocyanine green; staphylococcus epidermidis; barrier function; keratin-14; humans; human; female; article; claudin 4; breast cancer-related lymphedema; breast cancer lymphedema; inflammatory skin diseases; filaggrin; keratinocyte differentiation; filaggrin proteins; flg protein; tight junction protein; tjp1 protein, human |
| Journal Title: | Journal of Investigative Dermatology |
| Volume: | 145 |
| Issue: | 1 |
| ISSN: | 0022-202X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2025-01-01 |
| Start Page: | 85 |
| End Page: | 97.e4 |
| Language: | English |
| DOI: | 10.1016/j.jid.2024.05.017 |
| PUBMED: | 38879154 |
| PROVIDER: | scopus |
| PMCID: | PMC12043072 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK authors: Babak J. Mehrara -- Source: Scopus |
