Low Colorectal Tumor Removal by E-Cadherin Destruction-Enabled Tumor Cell Dissociation
0303 health sciences
03 medical and health sciences
Cell Line, Tumor
Tumor Microenvironment
Humans
Cadherins
Colorectal Neoplasms
Edetic Acid
3. Good health
DOI:
10.1021/acs.nanolett.1c04797
Publication Date:
2022-03-25T23:47:25Z
AUTHORS (9)
ABSTRACT
Treatments for low colorectal cancer (CRC) remain a great challenge due to the heavy physical and psychological burdens of colostomy, strong drug toxicity in chemotherapy, and myelosuppression-/chemoradiation-related gastrointestinal symptoms. In this study, a highly biosafe and effective tumor cell dissociation-based low CRC treatment modality has been verified on both PDOs in vitro and colorectal tumor models in vivo. Notably, controllable EDTA release at the tumor sites was achieved by the LDH degradation in response to a slightly acidic microenvironment of low CRC tumors. Resultantly, the intratumoral E-cadherin for intercellular junctions of low CRC tumors was effectively destroyed via Ca2+ depletion by released EDTA from the interlayers, initiating remarkable tumor cell dissociation and resultant tumor disaggregation/removal via defecation. Dissociated tumor cells were prevailingly enveloped by LDH/EDTA, which prevented them from readhering to adjacent tissues, providing an unprecedented, efficient and safe therapeutic modality for low CRC, which will benefit patients suffering low CRC.
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