Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro.

The invasion and migration occurring in primary neoplastic tissue explants were studied by using a three-dimensional collagen matrix model, subsequent time-lapse videomicroscopy, and computer-assisted cell tracking. We show that not only single cells but groups of clustered cells comprising 5 to more than 100 cells detach from the primary tumor lesion and migrate within the adjacent extracellular matrix. These clusters were highly polarized, resulting in a high directional persistence of migration. Locomoting cell clusters were observed in primary cultures from invasive oral squamous cell carcinomas (6 of 9), ductal breast carcinomas (2 of 3), and rhabdomyosarcoma (1 of 1), whereas normal oral mucosa (0 of 4) was cell cluster negative. Thus, locomoting cell clusters could be a novel and potentially important mechanism of cancer cell invasion and metastasis.

[1]  M. Abercrombie,et al.  Contact inhibition and malignancy , 1979, Nature.

[2]  L. Liotta,et al.  The significance of hematogenous tumor cell clumps in the metastatic process. , 1976, Cancer research.

[3]  P. Sträuli,et al.  Morphological studies on V2 carcinoma invasion and tumor-associated connective tissue changes in the rabbit mesentery. , 1983, Cancer research.

[4]  I. Talbot,et al.  Invasion of veins by carcinoma of rectum: method of detection, histological features and significance , 1981, Histopathology.

[5]  J. Starkey,et al.  Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines. , 1989, Cancer research.

[6]  L. Liotta,et al.  Biochemical interactions of tumor cells with the basement membrane. , 1986, Annual review of biochemistry.

[7]  P. Friedl,et al.  Lymphocyte locomotion in three-dimensional collagen gels. Comparison of three quantitative methods for analysing cell trajectories. , 1993, Journal of immunological methods.

[8]  D. Glaves.  Correlation between circulating cancer cells and incidence of metastases. , 1983, British Journal of Cancer.

[9]  A. Schor,et al.  The use of three‐dimensional collagen gels for the study of tumour cell invasion in vitro: Experimental parameters influencing cell migration into the gel matrix , 1982, International journal of cancer.

[10]  I. Carr.  Experimental lymphatic metastasis , 1983, Journal of microscopy.

[11]  M. Mareel,et al.  Effect of microtubule inhibitors on invasion and on related activities of tumor cells. , 1984, International review of cytology.

[12]  E. Kohn,et al.  Molecular insights into cancer invasion: strategies for prevention and intervention. , 1995, Cancer research.

[13]  H. Hirte,et al.  Factors determining the ability of cytokine-activated killer cells to lyse human ovarian carcinoma targets. , 1991, Cellular immunology.

[14]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[15]  P. Friedl,et al.  T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules. , 1995, Journal of immunology.

[16]  B. Zetter,et al.  In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. , 1991, Science.

[17]  S J Singer,et al.  The directed migration of eukaryotic cells. , 1986, Annual review of cell biology.