Proteomic molecular portrait of interface zone in breast cancer.
Surgical tumor margins are intended to encompass residual tumor cells but may not always accurately delineate the boundary between tumor and normal tissue. Efforts to define tumor margins based on molecular analysis have achieved limited success. Furthermore, no clinical trials have addressed the scope of the tumor microenvironment. Here, we considered the tumor cell population and surrounding microenvironment in delineating tumor margins, classifying breast cancer into tumor and normal zones, and introducing the concept of an interface zone, the region between the invading tumor front and normal tissue, which develops during tumor invasion and metastasis through remodeling of the tumor microenvironment. Pathological signatures of invasion markers in tumor tissues are most dynamic within the invading tumor front. We compared protein profiles of tumor, normal, and interface zones using MALDI-MS. Proteins upregulated in the interface zone were identified by peptide mass fingerprinting and confirmed by database searching with chemically assisted MALDI-PSD spectra. Upregulation was confirmed for RhoGDIα, CAPG, WDR1, and CK8 by Western and immunohistochemical analyses. Our results demonstrate that the molecular profile of the interface zone is unique and suggest that upregulation of proteins here may be related to progression and metastasis of breast carcinomas.
Kang
Suki
S
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Kim
Min Ju
MJ
An
Heejung
H
Kim
Baek Gil
BG
Choi
Yoon Pyo
YP
Kang
Kyu Sub
KS
Gao
Ming-Qing
MQ
Park
Hangran
H
Na
Hyung Jin
HJ
Kim
Hye Kyung
HK
Yun
Hae Ree
HR
Kim
Dong Su
DS
Cho
Nam Hoon
NH
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D008840:Microfilament Proteins; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins; D010449:Peptide Mapping; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D059016:Tumor Microenvironment; D015854:Up-Regulation; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D014408:Biomarkers, Tumor; D020730:Guanine Nucleotide Dissociation Inhibitors; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C118067:WDR1 protein, human; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C066575:CAPG protein, human