An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation

Jörg Haier, Timo Korb, Birgit Hotz, Hans Ullrich Spiegel, Norbert Senninger, Michael G. Sarr, Mathias G. Stelzner, Kevin E. Behrns, Reid B. Adams

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Organ-specific tumor cell adhesion within the microcirculation of host organs is an important step in the metastatic cascade. Circulating tumor cells have to adhere within the microcirculatory vessels, quickly stabilize their adhesion and probably leave the circulation to avoid toxic effects of hydrodynamic shear forces of circulating blood. Using intravital fluorescence microscopy we established a new model for the intravital observation of colon carcinoma cell adhesion within the hepatic microcirculation. HT-29 (human) and CC531 (rat) colon carcinoma cells were fluorescence labeled using CalceinAM. Single cell suspensions were injected intraarterially in Sprague-Dawley rats. Using intravital fluorescence microscopy adhesive interactions of circulating tumor cells within the hepatic microcirculation were observed at the liver surface. These interactions were analyzed regarding their time course and the localization within the vascular tree. Autofluorescence of liver parenchyma was sufficient for distinction of hepatic sinusoids. Intravital microscopy enabled the differentiation of early events in adhesion formation within hepatic sinosoids, adhesion stabilization, and extravasation of the tumor cells into the liver parenchyma. Tumor cell adhesion occurred almost exclusively within sinusoidal capillaries; however, the diameter of these vessels was usually larger than that of the tumor cells leaving remaining perfused lumen of the capillaries. Colon carcinoma cells rapidly migrated into the liver parenchyma after successful adhesion within the sinusoids. In contrast to common endpoint assays of the metastatic cascade, this in vivo model allows investigations of metastatic colon carcinoma cell adhesion within the liver microcirculation as specific steps during the formation of hematogenous metastasis and their underlying mechanisms.

Original languageEnglish (US)
Pages (from-to)507-515
Number of pages9
JournalJournal of Gastrointestinal Surgery
Volume7
Issue number4
DOIs
StatePublished - May 2003
Externally publishedYes

Fingerprint

Microcirculation
Cell Adhesion
Liver
Neoplasms
Colon
Carcinoma
Circulating Neoplastic Cells
Fluorescence Microscopy
Endpoint Determination
Poisons
Hydrodynamics
Adhesives
Blood Vessels
Sprague Dawley Rats
Suspensions
Fluorescence
Observation
Neoplasm Metastasis

Keywords

  • Cell adhesion
  • Colorectal carcinoma
  • Intravital microscopy
  • Microcirculation

ASJC Scopus subject areas

  • Surgery

Cite this

An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation. / Haier, Jörg; Korb, Timo; Hotz, Birgit; Spiegel, Hans Ullrich; Senninger, Norbert; Sarr, Michael G.; Stelzner, Mathias G.; Behrns, Kevin E.; Adams, Reid B.

In: Journal of Gastrointestinal Surgery, Vol. 7, No. 4, 05.2003, p. 507-515.

Research output: Contribution to journalArticle

Haier, J, Korb, T, Hotz, B, Spiegel, HU, Senninger, N, Sarr, MG, Stelzner, MG, Behrns, KE & Adams, RB 2003, 'An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation', Journal of Gastrointestinal Surgery, vol. 7, no. 4, pp. 507-515. https://doi.org/10.1016/S1091-255X(03)00023-4
Haier, Jörg ; Korb, Timo ; Hotz, Birgit ; Spiegel, Hans Ullrich ; Senninger, Norbert ; Sarr, Michael G. ; Stelzner, Mathias G. ; Behrns, Kevin E. ; Adams, Reid B. / An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation. In: Journal of Gastrointestinal Surgery. 2003 ; Vol. 7, No. 4. pp. 507-515.
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