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Proteomic profiling of stromal reprogramming in canine simple mammary carcinomas using laser-capture microdissected FFPE tissue

ABSTRACT: Cancer-associated stroma (CAS) profoundly influences development and progression of tumours including mammary carcinoma (mCA). Spontaneous canine simple mCA represent relevant models of human mCA, notably also with respect to CAS reprogramming. While transcriptomic changes in CAS of mCA are well described, it remains unclear to what extent these differences translate to the protein level. Therefore, we sought to gain insight into the proteomic changes in CAS and compare them with transcriptomic changes in the same tissue. To this end, we analysed CAS and matched normal stroma isolated by laser-capture microdissection (LCM) by LC-MS/MS in a cohort of 14 Formalin-fixed paraffin embedded (FFPE) canine mCAs that we had previously characterized using LCM-RNAseq. Our results reveal clear differences in protein abundance between CAS and normal stroma, which are characterised by changes in the extracellular matrix, the cytoskeleton, and cytokines such as TNF. While the proteomics-based analysis of LCM-FFPE tissue detects fewer targets than RNAseq, the protein and RNA levels show a decent degree of correlation, especially for the most deregulated targets. Moreover, the results from both approaches reveal a comparable picture with regards to pathway activation. Finally, we validate transcriptomic upregulation of LTBP2, IGFBP2, COL6A5, POSTN, FN1, COL4A1, COL12A1, PLOD2, COL4A2, and IGFBP7 in CAS on the protein level and demonstrate their adverse prognostic value for human breast cancer. Given the relevance of canine mCA as model for the human disease, our analysis substantiates these targets as disease-promoting stromal components with implications for breast cancer in both humans and dogs.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

TISSUE(S): Stroma, Stromal Cell

DISEASE(S): Breast Cancer

SUBMITTER: Laura Kunz

LAB HEAD: Enni Markkanen

PROVIDER: PXD023023 | Pride | 2021-03-30

REPOSITORIES: Pride

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Source:

			Action	DRS
	20191101_002_S206437_1_N_Control.raw	Raw
	20191101_003_S206455_11_N_Control.raw	Raw
	20191101_004_S206461_14_N_Control.raw	Raw
	20191101_005_S206449_8_N_Control.raw	Raw
	20191101_007_S206448_8_C_Diseased.raw	Raw

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Proteomic profiling of stromal reprogramming in canine simple mammary carcinomas using laser-capture microdissected FFPE tissue

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