The influence of the local environment on tissue architecture of colorectal carcinoma (CRC) cell aggregates and its consequence for tumour attack by lymphocytes in vitro and in vivo.
We analysed colorectal carcinoma (CRC) specimens, tumour cell spheroids and artificial tumours (ArTs) for tissue architecture, carcinoembryonic antigen (CEA) expression and lymphocyte infiltration. Two distinct organisation forms of well-differentiated CRC cells were found in vivo and in vitro. Tumour cells having contact with the tumour stroma in primary tumours, and tumour cells growing within a stroma-like structure in vitro (ArTs) were arranged as pseudoglands. In contrast, tumour cells grown as spheroids or tumour cells having lost contact with the tumour stroma in primary tumours, and most probably in the circulation, showed an inversion of the architecture of these pseudoglands, presenting their apical cell membrane to the environment. These different tumour cell formations affect lymphocytes attacking the tumour, which need contact with specific cellular membranes of polarised tumour cells, depending on the tumour architecture. Recently, we demonstrated that the CEA expression of CRC cells correlated with their resistance against LAK-cell lysis. Since CEA is mainly expressed on the apical membrane of the tumour cells, independent of the tissue architecture, the change from the pseudoglandular to the spheroid-like formation may represent an escape mechanism for malignant cells.
Kammerer
R
R
Institute of Immunobiology, University of Freiburg, Germany.
von Kleist
S
S
D002272:Carcinoembryonic Antigen / Q000032:analysis; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008954:Models, Biological; D018874:Spheroids, Cellular / Q000276:immunology / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology*
D002272:Carcinoembryonic Antigen