Hyaluronate and invasiveness of the rabbit V2 carcinoma.

Abstract

We propose that hyaluronate, a major component of extracellular matrices through which cells migrate during embryonic tissue development and in regenerative processes, is also concentrated in the environment through which neoplastic cells invade local host tissues and may facilitate this process. The hyaluronate content of invasive V2 carcinoma grown in rabbit was found to be 34 times greater than that of the same tumor grown in the nude mouse, in which it is noninvasive. Moreover, hyaluronate concentrations were most elevated in the connective tissue interface between the tumor mass and the neighboring host tissue in the invasive rabbit tumors. The particular site of tumor implantation in the rabbit or nude mouse did not affect the concentrations of hyaluronate in either the parenchyma or the surrounding connective tissue. Similar values were obtained for neoplasms grown in muscle, which normally contains little hyaluronate, and in subcutaneous tissue, which is relatively rich in this glycosaminoglycan. The extracellular environment through which cells migrate during embryonic development and repair processes is enriched in the glycosaminoglycan (GAG) hyaluronate. Examples are found in the developing embryonic cornea (1), sclerotome (2), neural crest (3-5), heart (6, 7), and primary mesenchyme (8), as well as in regenerating salamander limb (9), regenerating rabbit tendon (10), and bone fracture callus (11). In certain of these tissues-e.g., the embryonic cornea (1) and neural crest (3-5, 12)-a close correlation between high concentrations of hyaluronate, high levels of hydration, and increased matrix volume with cell migration has been observed. On the basis of these studies we have proposed (i) that, due to its unique hydrodynamic properties (13), hyaluronate exerts a swelling pressure that can cause alterations in the size of intercellular spaces and separation of cell and connective tissue layers, thus opening avenues for cell migration, and (ii) that hyaluronate binds to the surface of cells (14), influencing specific cell interactions that might regulate the timing of cell assembly and differentiation (for review, see ref. 15).We are now examining the proposition that tumor cell migration into neighboring host tissue (i.e., invasion) also requires a hyaluronate-enriched environment. Previous studies in this laboratory of the cellular source of collagenase in the V2 carcinoma compared this neoplasm in the rabbit with that in the nude mouse (C. Biswas, K. J. Bloch, and J. Gross, unpublished results). Histological examination showed infiltration of tumor cells into and beyond the surrounding connective tissue (here called "capsule") of the rabbit tumors but not that of the nude mouse tumors. The capsules of the latter appeared to be intact around the entire neoplasm whereas, in the rabbit, sections of the tumor-host interface were fused, giving rise to discontinuities in the capsule and infiltration of tumor cells. The rabbit intramuscular and subcutaneous tumors have also been shown to be reproduc...

Expression of hyaluronan synthase 2 or hyaluronidase 1 differentially affect the growth rate of transplantable colon carcinoma cell tumors

“…In many malignancies elevated levels of hyaluronan are correlated to increased metastasis. 42,43 In the present investigation, we studied the effects of overexpression of Has2 or Hyal1 on tumor growth rate in an experimental colon carcinoma model. Transfection of carcinoma cells with Has2 cDNA led to an increase in the rate of tumor growth in syngeneic rats, whereas transfection of Hyal1 cDNA suppressed the growth rate.…”

Hyaluronan: fundamental principles and applications in cancer

“…HYA has been related to cancer cell migration (invasion) in the V2 papillary carcinoma of rabbits [49]. The invasive (peripheral) areas in human cancer of the breast have a higher HYA content than central tumour areas [11].…”

The role of the lymphatic system in rabbit models for cancer metastasis research: a perspective from comparative anatomy

“…The conduit lymphatic vessels drain into several areas in the human adult diaphragmatic pleura: [1] towards the lower sternal portion; [2] to the boundary adjoining the intercostal pleura; [3] to the junction of the vertebrae and ribs; [4] to the aortic hiatus; and [5] to the esophageal hiatus (37). Furthermore, the mediastinal pleura drains into the following regions: [1] the upper and lower portions of the sternum; [2] the reflection region of the pericardium; [3] the hilum of the lung; [4] the aortic hiatus; and [5] the esophageal hiatus (37).…”

“…[1] Starling's hypothesis; [2] Fick's law of diffusion; [3] the serosal pressure associated with organ movement and posture; [4] active transport by mesothelial cells; and [5] a lymphatic drainage system via lymphatic stomata (30,31). Of these factors, the lymphatic drainage system via lymphatic stomata likely plays an important role (30)(31)(32)(33)(34), which may contribute up to approximately 75-80% of the fluid absorption rate in the abdominal and pleural cavities (33,35).…”

“…The rabbit is one of these species. The rabbit exhibits greater biological similarities to humans than the mouse or rat (1), and the rabbit VX2 allograft cancer model has been used in a broad range of oncological studies, such as stromal responses, metastatic behaviors and therapeutic effects (2)(3)(4)(5)(6)(7)(8)(9).…”