Cell detachment ratio on pH-responsive chitosan: A useful biometric for prognostic judgment and drug efficacy assessment in oncology

• Published in: Carbohydrate polymers Vol. 261; p. 117911
• Main Authors: Yen, Chia-Hsiang, Young, Tai-Horng, Huang, Tsung-Wei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2021
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Adhesion - drug effects; Cell adhesive strength; Cell detachment ratio; Cell Line, Tumor; Chitosan - chemistry; Chitosan - pharmacology; Drug efficacy; Female; Humans; Hydrogen-Ion Concentration; Integrin; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medical Oncology - methods; Mice; Mice, Nude; Particle Size; pH-responsive chitosan; Prognosis; Prognosis judgment; Treatment Outcome; Xenograft Model Antitumor Assays; Drug efficacy; pH-responsive chitosan; Integrin; Cell detachment ratio; Prognosis judgment; Cell adhesive strength
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2021.117911

•The biometric cell detachment ratio (CDR) is derived from the pH-responsive chitosan.•The cancer aggressiveness can be parameterized and expressed numerically as CDR.•In the same cancer cell line, a higher CDR represents greater aggressiveness.•The disease state can be defined by the CDR deviation compared to the naïve baseline.•CDR can be adopted as a clinical index for prognosis judgment and drug evaluation.
The inherently unpredictable complexity of tumors impedes the widespread practice of the molecular biomarkers in outcome prediction. Alternatively, from the biophysical perspective, this study sought to investigate the applicability of the cell detachment ratio (CDR) derived from pH-responsive chitosan as a biometrical identifier for the disease state in cancer prognostic judgment and drug efficacy assessment. In the targeted therapy model, the repression of tumor dissemination in cells harboring aberrant ErbB signals (human non-small cell lung cancer cell line PC9 and breast cancer cell line BT474) were first demonstrated both in vitro and in vivo. Consequently, the corresponding CDR profile goes synchronously with the extent of cancer regression in response to the medication. Definitive integrins that drive the cell detachment were also verified through CDR examination following the integrin functional blockade. Conclusively, CDR is a promising clinical index for evaluation of the metastatic cell behaviors in terms of the cell detachment.