Lymph Flow from Murine Footpad Tumors before and after Sublethal Hyperthermia

Abstract

The effect of local hyperthermia (43.5 degrees C for 1 h) on lymph flow from B16-F10 tumor-bearing foot pads of C57BL/6 mice was measured by monitoring the clearance of 99mTc-labeled human serum albumin. The foot was represented by a single-compartment model enabling a quantitative computation of lymphatic flow from the tumor to regional lymph nodes. Lymphatic flow from untreated tumors was 0.0059 +/- 0.0011 ml/min cm3 compared to 0.0118 +/- 0.0027 ml/min cm3 lymphatic flow from tumors immediately following heating. Morphological alterations in tumor blood vessels result in their high vascular permeability. The increase in lymphatic clearance from tumors after sublethal hyperthermia is compatible with the increase in interstitial fluid formation in tumors based on Starling's Law.

Sentinel lymph node metastasis in experimental melanoma: Relationships among primary tumor size, lymphatic vessel diameter and99mTc-labeled human serum albumin clearance

“…Initial studies conducted in our laboratory (20) measured [99mTc]HSA clearance from footpads, with and without tumor, in mice sacrificed at defined time periods. Radioactive counts in the footpad, SLNs, FLNs, and spleens were quantitated in a well-type gamma counter.…”

“…Anesthetized mice (n = 3 per group) were placed supine on a padded, lead-shielded board, and the fore-and hind paws were taped to the board without occluding the blood flow to the tumor. An assay of radiotracer clearance from the footpad of live mice using a NaL scintillation detector (models 802-3 and 2007P; Canberra, CT, USA) interfaced with an IBM-compatible personal computer was adapted from our previously described protocol (20). The detector crystal was fitted with a conic collimator 56.8 mm in diameter and 40.4 mm high with an aperture of 4.0 mm to limit the detected radiations exclusively to the RRF.…”

“…One of the radionuclides, 99mtechnetium-labeled human serum albumin ([99mTc]HSA), has also been effective for studying the rate of lymphatic clearance when injected into the center of mouse footpad melanomas (20). We devised a series of experiments to determine the relationship between clearance of [99mTc]HSA and the incidence of SLN and FLN metastasis.…”

Molecular mechanisms of metastasis

“…Sub-therapeutic hyperthermia [67] or radiation (unpublished observations) to footpad-implanted F16 melanomas in C57BL/6 mice induces an increase in lymph flow from tumors. Such an increase is associated with an increase in metastasis [68].…”

The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

“…27,28 High intratumoral interstitial fluid pressure (IFP), caused by abnormal structure and function of blood and lymphatic vessels in tumors, results in significant fluid convection near the tumor margin, creating peritumoral edema, transport of tumor-derived molecules and cells that generate lymphangiogenesis and angiogenesis, and increased lymphatic flow. 21,[27][28][29][30][31] Interstitial hypertension compresses blood vessels but, because of anchoring filaments that tether LECs to surrounding stromal tissues, and overlapping endothelial cells that open up gaps in the lymphatic capillary wall, lymphatic lumena may remain open despite the increased pressure and mechanically enhance the intravasation of fluid and tumor cells. 28,32 The low-shear lymphatic system is also less likely to cause mechanical destruction of tumor cells than the high-shear blood circulation.…”