Intratumor Heterogeneity in Interstitial Fluid Pressure in Cervical and Pancreatic Carcinoma Xenografts

Abstract

Preclinical studies have suggested that interstitial fluid pressure (IFP) is uniformly elevated in the central region of tumors, whereas clinical studies have revealed that IFP may vary among different measurement sites in the tumor center. IFP measurements are technically difficult, and it has been claimed that the intratumor heterogeneity in IFP reported for human tumors is due to technical problems. The main purpose of this study was to determine conclusively whether IFP may be heterogeneously elevated in the central tumor region, and if so, to reveal possible mechanisms and possible consequences. Tumors of two xenograft models were included in the study: HL-16 cervical carcinoma and Panc-1 pancreatic carcinoma. IFP was measured with Millar SPC 320 catheters in two positions in each tumor and related to tumor histology or the metastatic status of the host mouse. Some tumors of both models showed significant intratumor heterogeneity in IFP, and this heterogeneity was associated with a compartmentalized histological appearance (i.e., the tissue was divided into compartments separated by thick connective tissue bands) in HL-16 tumors and with a dense collagen-I-rich extracellular matrix in Panc-1 tumors, suggesting that these connective tissue structures prevented efficient interstitial convection. Furthermore, some tumors of both models developed lymph node metastases, and of the two IFP values measured in each tumor, only the higher value was significantly higher in metastatic than in non-metastatic tumors, suggesting that metastatic propensity was determined by the tumor region having the highest IFP.

Targeting Fluorescence Imaging of RGD-Modified Indocyanine Green Micelles on Gastric Cancer

“…To address these challenges, numbers of carriers are introduced to encapsulate ICG that protect it from non-specific binding of plasma protein, provide enhanced stability and tumor targeting (i.e., permeability and retention effect, EPR). Nevertheless, in some solid tumors such as GC, since the interstitial fluid pressure is often increased (Yonucu et al, 2017;Hansem et al, 2019), it's hard for these nanoparticles to permeate from leak tumor endothelial cells and largely transfer to the tumor sites. Therefore, challenges remain to improve the ability to penetration and targeting of the tumor.…”

Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine

“…1A). The IFP is elevated from -3-3 mmHg in healthy tissues to 10-100 mmHg in tumor tissues due to the irregular structure and elevated permeability of vasculature, disordered blood flow, stiffened interstitial matrix, and the impaired drainage function of lymphatic vessels [97][98][99]. High IFP is closely associated with poor prognosis and survival of cancer patients.…”

Noninvasive Estimation of Tumor Interstitial Fluid Pressure from Subharmonic Scattering of Ultrasound Contrast Microbubbles

“…The linear array transducer with 128 elements had a center frequency of 8 MHz and a −6 dB bandwidth of 4 MHz to 12 MHz. According to previous theoretical and experimental studies, the optimal transmit frequency of the subharmonic scattering was twice the resonance frequency of the UCA microbubbles [33,34]. The transmitted frequency of the experiment was selected according to the Sonazoid's resonance frequency from the acoustic attenuation measurement.…”