Peritoneal Metastasis in Colorectal Cancer: hyaluronic acid dependent adhesion

Abstract Introduction Peritoneal Metastasis (PM) in Colorectal Cancer (CRC) undoubtedly remains a challenge to treat and often portends a poor prognosis for patients. Hyaluronic acid (HA) is found throughout the body, including coating of the peritoneum. Interaction of HA with HA-dependent adhesion molecules can facilitate cell adhesion within the peritoneum. HA may play a role in spread of PM in CRC in association with known HA-receptor molecules CD44, RHAMM and ICAM-1. Method Expression of HA-dependent and HA-independent adhesion molecules were examined in CRC using tissue microarray datasets and matched to clinicopathological data. In-vitro peritoneal modelling assessed cellular adhesion when treated with a competitive HA-inhibitor (HAi) or excess exogenous HA. An in-vivo Xenograft peritoneal model, using CD1 nude mice injected with CRC cells, were treated with either HAi or excess exogenous HA and compared to a control (PPL: PE9445FC2). Result There is a significant increase in expression of HA-dependent adhesion molecules seen in CD44, RHAMM and ICAM-1 in CRC (p=<0.0001). Whilst Non-HA-dependent adhesion molecules demonstrated either significant downregulation or no expression difference. Cellular adhesion was decreased in three CRC cell lines when treated with HAi or excess HA. Treatment with HAi and HA in-vivo confirmed a significant reduction in PM, compared to controls (HAi p=0.0094, HA p=0.0009). Conclusion HA-dependent adhesion molecules and HA appear to play a role in CRC. Targeting HA-dependent interaction in CRC influences cellular adhesion and may have a potential therapeutic use in treatment of PM in CRC. Further in-vitro and in vivo modelling is needed. Take-home message HA receptor adhesion molecules CD44, RHAMM and ICAM-1 have all been independently implicated in adverse outcomes in colorectal cancer. Targeting HA receptor interaction appears to reduce peritoneal dissemination in colorectal cancer.

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Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Colorectal Cancer

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0040-1714242 ◽

2020 ◽

Vol 33 (06) ◽

pp. 372-376

Author(s):

Hideaki Yano

Keyword(s):

Colorectal Cancer ◽

Intraperitoneal Chemotherapy ◽

Cytoreductive Surgery ◽

Peritoneal Metastasis ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Peritoneal Cancer Index ◽

Systemic Disease ◽

Good Reason ◽

Standard Of Care ◽

Peritoneal Cancer

AbstractPeritoneal metastasis from colorectal cancer (PM-CRC) is used to be considered a systemic and fatal condition; however, it has been growingly accepted that PM-CRC can still be local disease rather than systemic disease as analogous to liver or lung metastasis.Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now considered an optimal treatment for PM-CRC with accumulating evidence. There is a good reason that CRS + HIPEC, widely accepted as a standard of care for pseudomyxoma peritonei (PMP), could be a viable option for PM-CRC given a similarity between PM-CRC and PMP.Recent years have also seen that modern systemic chemotherapy with or without molecular targeted agents can be effective for PM-CRC. It is possible that neoadjuvant or adjuvant chemotherapy combined with CRS + HIPEC could further improve outcomes.Patient selection, utilizing modern images and increasingly laparoscopy, is crucial. Particularly, diagnostic laparoscopy is likely to play a significant role in predicting the likelihood of achieving complete cytoreduction and assessing the peritoneal cancer index score.

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Prognostic Significance of Peritoneal Metastasis in Stage IV Colorectal Cancer Patients With R0 Resection

Diseases of the Colon & Rectum ◽

10.1097/dcr.0000000000000858 ◽

2017 ◽

Vol 60 (10) ◽

pp. 1041-1049 ◽

Cited By ~ 5

Author(s):

Keiichi Arakawa ◽

Kazushige Kawai ◽

Soichiro Ishihara ◽

Keisuke Hata ◽

Hiroaki Nozawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Peritoneal Metastasis ◽

Prognostic Significance ◽

Stage Iv ◽

R0 Resection ◽

Stage Iv Colorectal Cancer ◽

Colorectal Cancer Patients

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Targeting Hyaluronic Acid and Peritoneal Dissemination in Colorectal Cancer

Clinical Colorectal Cancer ◽

10.1016/j.clcc.2021.11.008 ◽

2021 ◽

Author(s):

Mr Faris Soliman ◽

Dr Lin Ye ◽

Dr Wenguo Jiang ◽

Miss Rachel Hargest

Keyword(s):

Colorectal Cancer ◽

Hyaluronic Acid ◽

Peritoneal Dissemination

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Thermosensitive In Situ Gel Containing Luteolin Micelles is a Promising Efficient Agent for Colorectal Cancer Peritoneal Metastasis Treatment

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2020.2870 ◽

2020 ◽

Vol 16 (1) ◽

pp. 54-64 ◽

Cited By ~ 1

Author(s):

Yuzhu Hu ◽

Xiaoye Chen ◽

Zongyuan Li ◽

Songping Zheng ◽

Yongzhong Cheng

Keyword(s):

Colorectal Cancer ◽

Drug Release ◽

Peritoneal Metastasis ◽

Water Solubility ◽

Local Therapy ◽

Cancer Drug ◽

Poly Ethylene ◽

Vegetables And Fruits

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.

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Prognostic Impact of Macroscopic Complete Resection and Inflammatory Status for Colorectal Cancer With Peritoneal Dissemination

International Surgery ◽

10.9738/intsurg-d-18-00009.1 ◽

2018 ◽

Vol 103 (7-8) ◽

pp. 331-338

Author(s):

Satoru Yamaguchi ◽

Keisuke Ihara ◽

Yosuke Shida ◽

Haruka Yokoyama ◽

Hideo Ogata ◽

...

Keyword(s):

Colorectal Cancer ◽

Peritoneal Metastasis ◽

Peritoneal Dissemination ◽

Prognostic Score ◽

Case Series ◽

Glasgow Prognostic Score ◽

Carbohydrate Antigen ◽

Complete Resection ◽

Prognostic Impact ◽

Inflammatory Status

Objective: To clarify the appropriate treatment policy for colorectal cancer with peritoneal metastasis, case series were analyzed retrospectively. Summary of background data: The frequency of colorectal cancer and peritoneal dissemination occurring simultaneously is 4% to 7%. The prevention of peritoneal metastasis and the development of a strategy for cure are considered important factors in improving the treatment outcome of colorectal cancer. Methods: A total of 60 patients with colorectal cancer with peritoneal dissemination were enrolled in this study. Tumor and host condition characteristics and treatment regimens affecting patient survival were tested by using Kaplan-Meier survival analysis. Results: Histologic type, carbohydrate antigen 19-9, macroscopic complete resection, and Glasgow Prognostic Score were found to be independent prognostic factors for overall survival. Conclusions: Peritoneal carcinomatosis can result in better patient prognoses in patients with well-differentiated carcinoma, less peritoneal spread, low levels of tumor markers, and a low Glasgow Prognostic Score. In these patients, curative resection of peritoneal metastases followed by intensive chemotherapy might be effective.

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