Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition

Wesley Poon; Rania Uzma; Reid Master; Lin Wang; Ashok Veeraraghavan; Lisa A. Ridnour; Stephen J. Lockett; Jenny C. Chang; Hong Zhao; Raksha Raghunathan; David A. Wink; Stephen T. Wong

doi:10.1117/12.3080654

Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition

Wesley Poon, Rania Uzma, Reid Master, Lin Wang, Ashok Veeraraghavan, Lisa A. Ridnour, Stephen J. Lockett, Jenny C. Chang, Hong Zhao, Raksha Raghunathan, David A. Wink, Stephen T. Wong

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype that lacks targetable receptors, limiting the availability of effective treatments. The tumor microenvironment of TNBC is highly heterogenous characterized by high immune infiltration, elevated inflammatory signaling, extracellular matrix (ECM) disorganization, and individual niches of tumor cells. Nitric oxide synthase-2 (NOS2) is an upregulated enzyme in TNBC which produces nitric oxide and contributes to the inflammatory and pro-tumorigenic microenvironment. Cyclooxygenase-2 (COX-2) produces pro-inflammatory and pro-NOS2 signaling molecules which further support tumor growth. Thus, the impact of diminished NOS2 and COX-2 activity in TNBC is of particular interest. We employ label-free, high resolution, multimodal multiphoton microscopy consisting of second harmonic generation (SHG), two-photon autofluorescence (TPAF), and coherent anti-Stokes Raman scattering (CARS) imaging to investigate changes in the TNBC tumor microenvironment including collagen structure, metabolic state, and lipid storage under conditions of modified NOS2 and COX-2 functioning.

Original language	English (US)
Title of host publication	Multiphoton Microscopy in the Biomedical Sciences XXVI
Editors	Ammasi Periasamy, Peter T. C. So, Karsten Konig
Publisher	SPIE
ISBN (Electronic)	9781510696259
DOIs	https://doi.org/10.1117/12.3080654
State	Published - Mar 5 2026
Event	26th Multiphoton Microscopy in the Biomedical Sciences - San Francisco, United States Duration: Jan 18 2026 → Jan 20 2026

Publication series

Name	Proceedings of SPIE - The International Society for Optical Engineering
Volume	13856
ISSN (Print)	0277-786X
ISSN (Electronic)	1996-756X

Conference

Conference	26th Multiphoton Microscopy in the Biomedical Sciences
Country/Territory	United States
City	San Francisco
Period	1/18/26 → 1/20/26

Keywords

coherent anti-Stokes Raman scattering
COX-2
multiphoton microscopy
NOS2
second harmonic generation
triple negative breast cancer
two-photon autofluorescence

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
Instrumentation
Condensed Matter Physics
Computer Science Applications
Applied Mathematics
Electrical and Electronic Engineering

Access to Document

10.1117/12.3080654

Cite this

Poon, W., Uzma, R., Master, R., Wang, L., Veeraraghavan, A., Ridnour, L. A., Lockett, S. J., Chang, J. C., Zhao, H., Raghunathan, R., Wink, D. A., & Wong, S. T. (2026). Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition. In A. Periasamy, P. T. C. So, & K. Konig (Eds.), Multiphoton Microscopy in the Biomedical Sciences XXVI Article 138560D (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 13856). SPIE. https://doi.org/10.1117/12.3080654

Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition. / Poon, Wesley; Uzma, Rania; Master, Reid et al.
Multiphoton Microscopy in the Biomedical Sciences XXVI. ed. / Ammasi Periasamy; Peter T. C. So; Karsten Konig. SPIE, 2026. 138560D (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 13856).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Poon, W, Uzma, R, Master, R, Wang, L, Veeraraghavan, A, Ridnour, LA, Lockett, SJ, Chang, JC , Zhao, H , Raghunathan, R, Wink, DA & Wong, ST 2026, Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition. in A Periasamy, PTC So & K Konig (eds), Multiphoton Microscopy in the Biomedical Sciences XXVI., 138560D, Proceedings of SPIE - The International Society for Optical Engineering, vol. 13856, SPIE, 26th Multiphoton Microscopy in the Biomedical Sciences, San Francisco, United States, 1/18/26. https://doi.org/10.1117/12.3080654

Poon W, Uzma R, Master R, Wang L, Veeraraghavan A, Ridnour LA et al. Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition. In Periasamy A, So PTC, Konig K, editors, Multiphoton Microscopy in the Biomedical Sciences XXVI. SPIE. 2026. 138560D. (Proceedings of SPIE - The International Society for Optical Engineering). doi: 10.1117/12.3080654

Poon, Wesley ; Uzma, Rania ; Master, Reid et al. / Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition. Multiphoton Microscopy in the Biomedical Sciences XXVI. editor / Ammasi Periasamy ; Peter T. C. So ; Karsten Konig. SPIE, 2026. (Proceedings of SPIE - The International Society for Optical Engineering).

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title = "Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition",

abstract = "Triple negative breast cancer (TNBC) is an aggressive subtype that lacks targetable receptors, limiting the availability of effective treatments. The tumor microenvironment of TNBC is highly heterogenous characterized by high immune infiltration, elevated inflammatory signaling, extracellular matrix (ECM) disorganization, and individual niches of tumor cells. Nitric oxide synthase-2 (NOS2) is an upregulated enzyme in TNBC which produces nitric oxide and contributes to the inflammatory and pro-tumorigenic microenvironment. Cyclooxygenase-2 (COX-2) produces pro-inflammatory and pro-NOS2 signaling molecules which further support tumor growth. Thus, the impact of diminished NOS2 and COX-2 activity in TNBC is of particular interest. We employ label-free, high resolution, multimodal multiphoton microscopy consisting of second harmonic generation (SHG), two-photon autofluorescence (TPAF), and coherent anti-Stokes Raman scattering (CARS) imaging to investigate changes in the TNBC tumor microenvironment including collagen structure, metabolic state, and lipid storage under conditions of modified NOS2 and COX-2 functioning.",

keywords = "coherent anti-Stokes Raman scattering, COX-2, multiphoton microscopy, NOS2, second harmonic generation, triple negative breast cancer, two-photon autofluorescence",

author = "Wesley Poon and Rania Uzma and Reid Master and Lin Wang and Ashok Veeraraghavan and Ridnour, \{Lisa A.\} and Lockett, \{Stephen J.\} and Chang, \{Jenny C.\} and Hong Zhao and Raksha Raghunathan and Wink, \{David A.\} and Wong, \{Stephen T.\}",

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AU - Uzma, Rania

AU - Master, Reid

AU - Wang, Lin

AU - Veeraraghavan, Ashok

AU - Ridnour, Lisa A.

AU - Lockett, Stephen J.

AU - Chang, Jenny C.

AU - Zhao, Hong

AU - Raghunathan, Raksha

AU - Wink, David A.

AU - Wong, Stephen T.

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N2 - Triple negative breast cancer (TNBC) is an aggressive subtype that lacks targetable receptors, limiting the availability of effective treatments. The tumor microenvironment of TNBC is highly heterogenous characterized by high immune infiltration, elevated inflammatory signaling, extracellular matrix (ECM) disorganization, and individual niches of tumor cells. Nitric oxide synthase-2 (NOS2) is an upregulated enzyme in TNBC which produces nitric oxide and contributes to the inflammatory and pro-tumorigenic microenvironment. Cyclooxygenase-2 (COX-2) produces pro-inflammatory and pro-NOS2 signaling molecules which further support tumor growth. Thus, the impact of diminished NOS2 and COX-2 activity in TNBC is of particular interest. We employ label-free, high resolution, multimodal multiphoton microscopy consisting of second harmonic generation (SHG), two-photon autofluorescence (TPAF), and coherent anti-Stokes Raman scattering (CARS) imaging to investigate changes in the TNBC tumor microenvironment including collagen structure, metabolic state, and lipid storage under conditions of modified NOS2 and COX-2 functioning.

AB - Triple negative breast cancer (TNBC) is an aggressive subtype that lacks targetable receptors, limiting the availability of effective treatments. The tumor microenvironment of TNBC is highly heterogenous characterized by high immune infiltration, elevated inflammatory signaling, extracellular matrix (ECM) disorganization, and individual niches of tumor cells. Nitric oxide synthase-2 (NOS2) is an upregulated enzyme in TNBC which produces nitric oxide and contributes to the inflammatory and pro-tumorigenic microenvironment. Cyclooxygenase-2 (COX-2) produces pro-inflammatory and pro-NOS2 signaling molecules which further support tumor growth. Thus, the impact of diminished NOS2 and COX-2 activity in TNBC is of particular interest. We employ label-free, high resolution, multimodal multiphoton microscopy consisting of second harmonic generation (SHG), two-photon autofluorescence (TPAF), and coherent anti-Stokes Raman scattering (CARS) imaging to investigate changes in the TNBC tumor microenvironment including collagen structure, metabolic state, and lipid storage under conditions of modified NOS2 and COX-2 functioning.

KW - coherent anti-Stokes Raman scattering

KW - COX-2

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KW - NOS2

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KW - two-photon autofluorescence

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Spatially resolved, label-free multimodal multiphoton imaging reveals inflammation-induced lipid remodeling in triple-negative breast cancer following NOS2 inactivation and COX-2 inhibition

Abstract

Publication series

Conference

Keywords

ASJC Scopus subject areas

Access to Document

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