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EGFR modulates complement activation in head and neck squamous cell carcinoma

Abu-Humaidan, Anas H.A. LU orcid ; Ekblad, Lars LU orcid ; Wennerberg, Johan LU orcid and Sørensen, Ole E. LU (2020) In BMC Cancer 20(1).
Abstract

Background: The epidermal growth factor receptor (EGFR) is pivotal for growth of epithelial cells and is overexpressed in several epithelial cancers like head and neck squamous cell carcinoma (HNSCC). EGFR signalling is also involved in diverse innate immune functions in epithelia. We previously found a role for EGFR in modulating the complement system in skin, this prompted an investigation into EGFR role in complement modulation in HNSCC. Methods: We used patient derived HNSCC cell lines with varying sensitivities to EGFR inhibitors, and generated EGFR inhibition resistant cell lines to study the role of EGFR in modulating complement in HNSCC. Results: We found that HNSCC cell lines activate the complement system when incubated with... (More)

Background: The epidermal growth factor receptor (EGFR) is pivotal for growth of epithelial cells and is overexpressed in several epithelial cancers like head and neck squamous cell carcinoma (HNSCC). EGFR signalling is also involved in diverse innate immune functions in epithelia. We previously found a role for EGFR in modulating the complement system in skin, this prompted an investigation into EGFR role in complement modulation in HNSCC. Methods: We used patient derived HNSCC cell lines with varying sensitivities to EGFR inhibitors, and generated EGFR inhibition resistant cell lines to study the role of EGFR in modulating complement in HNSCC. Results: We found that HNSCC cell lines activate the complement system when incubated with human serum. This complement activation was increased in cell lines sensitive to EGFR inhibition following the use of the tyrosine kinase inhibitor Iressa. Sensitive cell line made resistant to EGFR-inhibitors displayed complement activation and a decrease in complement regulatory proteins even in the absence of EGFR-inhibitors. Complement activation did not cause lysis of HNSCC cells, and rather led to increased extracellular signal-regulated kinase (ERK) phosphorylation in one cell line. Conclusion: These data indicate that EGFR has a complement modulatory role in HNSCC, and that a prolonged EGFR-inhibition treatment in sensitive cancer cells increases complement activation. This has implications in understanding the response to EGFR inhibitors, in which resistance and inflammatory skin lesions are two major causes for treatment cessation.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer microenvironment, Complement activation, Complement regulation, EGFR, HNSCC, Iressa, Tyrosine kinase inhibitor
in
BMC Cancer
volume
20
issue
1
article number
121
publisher
BioMed Central (BMC)
external identifiers
  • pmid:32054454
  • scopus:85079339327
ISSN
1471-2407
DOI
10.1186/s12885-020-6615-z
language
English
LU publication?
yes
id
390f8e2b-b88e-4fff-87c7-536c05af7816
date added to LUP
2020-11-04 16:28:55
date last changed
2024-03-05 12:51:01
@article{390f8e2b-b88e-4fff-87c7-536c05af7816,
  abstract     = {{<p>Background: The epidermal growth factor receptor (EGFR) is pivotal for growth of epithelial cells and is overexpressed in several epithelial cancers like head and neck squamous cell carcinoma (HNSCC). EGFR signalling is also involved in diverse innate immune functions in epithelia. We previously found a role for EGFR in modulating the complement system in skin, this prompted an investigation into EGFR role in complement modulation in HNSCC. Methods: We used patient derived HNSCC cell lines with varying sensitivities to EGFR inhibitors, and generated EGFR inhibition resistant cell lines to study the role of EGFR in modulating complement in HNSCC. Results: We found that HNSCC cell lines activate the complement system when incubated with human serum. This complement activation was increased in cell lines sensitive to EGFR inhibition following the use of the tyrosine kinase inhibitor Iressa. Sensitive cell line made resistant to EGFR-inhibitors displayed complement activation and a decrease in complement regulatory proteins even in the absence of EGFR-inhibitors. Complement activation did not cause lysis of HNSCC cells, and rather led to increased extracellular signal-regulated kinase (ERK) phosphorylation in one cell line. Conclusion: These data indicate that EGFR has a complement modulatory role in HNSCC, and that a prolonged EGFR-inhibition treatment in sensitive cancer cells increases complement activation. This has implications in understanding the response to EGFR inhibitors, in which resistance and inflammatory skin lesions are two major causes for treatment cessation.</p>}},
  author       = {{Abu-Humaidan, Anas H.A. and Ekblad, Lars and Wennerberg, Johan and Sørensen, Ole E.}},
  issn         = {{1471-2407}},
  keywords     = {{Cancer microenvironment; Complement activation; Complement regulation; EGFR; HNSCC; Iressa; Tyrosine kinase inhibitor}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cancer}},
  title        = {{EGFR modulates complement activation in head and neck squamous cell carcinoma}},
  url          = {{http://dx.doi.org/10.1186/s12885-020-6615-z}},
  doi          = {{10.1186/s12885-020-6615-z}},
  volume       = {{20}},
  year         = {{2020}},
}